Novel, male-produced aggregation pheromone of the cerambycid beetle Rosalia alpina, a priority species of European conservation concern

PubMed Central

Zou, Yunfan; Hoskovec, Michal; Vrezec, Al; Stritih, Nataša; Millar, Jocelyn G.

2017-01-01

Several recent studies have demonstrated the great potential for exploiting semiochemicals in ecology and conservation studies. The cerambycid beetle Rosalia alpina represents one of the flagship species of saproxylic insect biodiversity in Europe. In recent years its populations appear to have declined substantially, and its range has shrunk considerably as a result of forest management and urbanization. Here, we collected volatile chemicals released by males and females of R. alpina. Analyses of the resulting extracts revealed the presence of a single male-specific compound, identified as a novel alkylated pyrone structure. In field bioassays in Slovenia, traps baited with the synthesized pyrone captured both sexes of R. alpina, indicating that the pyrone functions as an aggregation pheromone. Our results represent the first example of a new structural class of pheromones within the Cerambycidae, and demonstrate that pheromone-baited traps can provide a useful tool for sampling R. alpina. This tool could be particularly useful in the ongoing development of conservation strategies for the iconic but endangered Alpine longicorn. PMID:28827817

Evaluation of the antioxidant and cytotoxic activity of arzanol, a prenylated alpha-pyrone-phloroglucinol etherodimer from Helichrysum italicum subsp.microphyllum.

PubMed

Rosa, Antonella; Deiana, Monica; Atzeri, Angela; Corona, Giulia; Incani, Alessandra; Melis, M Paola; Appendino, Giovanni; Dessì, M Assunta

2007-01-30

Various phenolics and (mero)terpenoids from Helichrysum italicum subsp. microphyllum, a plant endemic to Sardinia, were investigated for their capacity to inhibit non-enzymatic lipid peroxidation. These compounds were studied in simple in vitro systems, under conditions of autoxidation and of iron (EDTA)-mediated oxidation of linoleic acid at 37 degrees C. Arzanol, a pyrone-phloroglucinol etherodimer, and helipyrone, a dimeric pyrone, showed antioxidant activity, and could protect linoleic acid against free radical attack in assays of autoxidation and EDTA-mediated oxidation. Methylarzanol, as well as the sesquiterpene alcohol rosifoliol, showed a decreased, but still significant, protective effect against linoleic acid oxidation. Arzanol and helipyrone were also tested in an assay of thermal (140 degrees C) autoxidation of cholesterol, where arzanol showed significant antioxidant activity. The cytotoxicity of arzanol was further evaluated in VERO cells, a line of fibroblasts derived from monkey kidney. Arzanol, at non-cytotoxic concentrations, showed a strong inhibition of TBH-induced oxidative stress in VERO cells. The results of the present work suggest that the natural compound arzanol exerts useful antioxidant properties in different in vitro systems of lipid peroxidation.

Functional characterization and expression of GASCL1 and GASCL2, two anther-specific chalcone synthase like enzymes from Gerbera hybrida.

PubMed

Kontturi, Juha; Osama, Raisa; Deng, Xianbao; Bashandy, Hany; Albert, Victor A; Teeri, Teemu H

2017-02-01

The chalcone synthase superfamily consists of type III polyketidesynthases (PKSs), enzymes responsible for producing plant secondary metabolites with various biological and pharmacological activities. Anther-specific chalcone synthase-like enzymes (ASCLs) represent an ancient group of type III PKSs involved in the biosynthesis of sporopollenin, the main component of the exine layer of moss spores and mature pollen grains of seed plants. In the latter, ASCL proteins are localized in the tapetal cells of the anther where they participate in sporopollenin biosynthesis and exine formation within the locule. It is thought that the enzymes responsible for sporopollenin biosynthesis are highly conserved, and thus far, each angiosperm species with a genome sequenced has possessed two ASCL genes, which in Arabidopsis thaliana are PKSA and PKSB. The Gerbera hybrida (gerbera) PKS protein family consists of three chalcone synthases (GCHS1, GCHS3 and GCHS4) and three 2-pyrone synthases (G2PS1, G2PS2 and G2PS3). In previous studies we have demonstrated the functions of chalcone synthases in flavonoid biosynthesis, and the involvement of 2-pyrone synthases in the biosynthesis of antimicrobial compounds found in gerbera. In this study we expanded the gerbera PKS-family by functionally characterizing two gerbera ASCL proteins. In vitro enzymatic studies using purified recombinant proteins showed that both GASCL1 and GASCL2 were able to use medium and long-chain acyl-CoA starters and perform two to three condensation reactions of malonyl-CoA to produce tri- and tetraketide 2-pyrones, usually referred to as alpha-pyrones in sporopollenin literature. Both GASCL1 and GASCL2 genes were expressed only in floral organs, with most expression observed in anthers. In the anthers, transcripts of both genes showed strict tapetum-specific localization. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antimicrobial phenolics and unusual glycerides from Helichrysum italicum subsp. microphyllum.

PubMed

Taglialatela-Scafati, Orazio; Pollastro, Federica; Chianese, Giuseppina; Minassi, Alberto; Gibbons, Simon; Arunotayanun, Warunya; Mabebie, Blessing; Ballero, Mauro; Appendino, Giovanni

2013-03-22

During a large-scale isolation campaign for the heterodimeric phloroglucinyl pyrone arzanol (1a) from Helichrysum italicum subsp. microphyllum, several new phenolics as well as an unusual class of lipids named santinols (5a-c, 6-8) have been characterized. Santinols are angeloylated glycerides characterized by the presence of branched acyl- or keto-acyl chains and represent a hitherto unreported class of plant lipids. The antibacterial activity of arzanol and of a selection of Helichrysum phenolics that includes coumarates, benzofurans, pyrones, and heterodimeric phloroglucinols was evaluated, showing that only the heterodimers showed potent antibacterial action against multidrug-resistant Staphylococcus aureus isolates. These observations validate the topical use of Helichrysum extracts to prevent wound infections, a practice firmly established in the traditional medicine of the Mediterranean area.

Polyunsaturated C-Glycosidic 4-Hydroxy-2-pyrone Derivatives: Total Synthesis Shows that Putative Orevactaene Is Likely Identical with Epipyrone A.

PubMed

Preindl, Johannes; Schulthoff, Saskia; Wirtz, Conny; Lingnau, Julia; Fürstner, Alois

2017-06-19

Orevactaene and epipyrone A were previously thought to comprise the same polyunsaturated tail but notably different C-glycosylated 4-hydroxy-2-pyrone head groups. Total synthesis now shows that the signature bicyclic framework assigned to orevactaene is a chimera; the compound is almost certainly identical with epipyrone A, whose previously unknown stereochemistry has also been established during this study. Key to success was the ready formation of the bicyclic core of putative orevactaene by a sequence of two alkyne cycloisomerization reactions using tungsten and gold catalysis. Equally important was the flexibility in the assembly process gained by the use of heterobimetallic polyunsaturated modules whose termini could be selectively and consecutively addressed in a practical one-pot cross-coupling sequence. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Theoretical study of the hydrolysis mechanism of 2-pyrone-4,6-dicarboxylate (PDC) catalyzed by LigI.

PubMed

Zhang, Shujun; Ma, Guangcai; Liu, Yongjun; Ling, Baoping

2015-09-01

2-Pyrone-4,6-dicarboxylate lactonase (LigI) is the first identified enzyme from amidohydrolase superfamily that does not require a divalent metal ion for catalytic activity. It catalyzes the reversible hydrolysis of 2-pyrone-4,6-dicarboxylate (PDC) to 4-oxalomesaconate (OMA) and 4-carboxy-2-hydroxymuconate (CHM) in the degradation of lignin. In this paper, a combined quantum mechanics and molecule mechanics (QM/MM) approach was employed to study the reaction mechanism of LigI from Sphingomonas paucimobilis. According to the results of our calculations, the whole catalytic reaction contains three elementary steps, including the nucleophilic attack, the cleavage of CO of lactone (substrate) and the intramolecular proton transfer. The intermediate has two intramolecular proton transfer pathways, due to which, two final hydrolysis products can be obtained. The energy profile indicates that 4-carboxy-2-hydroxymuconate (CHM) is the main hydrolysis product, therefore, the isomerization between 4-carboxy-2-hydroxymuconate (CHM) and 4-oxalomesaconate (OMA) is suggested to occur in solvent. During the catalytic reaction, residue Asp248 acts as a general base to activate the hydrolytic water molecule. Although His31, His33 and His180 do not directly participate in the chemical process, they play assistant roles by forming electrostatic interactions with the substrate and its involved species in activating the carbonyl group of the substrate and stabilizing the intermediates and transition states. Copyright © 2015 Elsevier Inc. All rights reserved.

The structure of poly(carbonsuboxide) on the atomic scale: a solid-state NMR study.

PubMed

Schmedt auf der Günne, Jörn; Beck, Johannes; Hoffbauer, Wilfried; Krieger-Beck, Petra

2005-07-18

In this contribution we present a study of the structure of amorphous poly(carbonsuboxide) (C3O2)x by 13C solid-state NMR spectroscopy supported by infrared spectroscopy and chemical analysis. Poly(carbonsuboxide) was obtained by polymerization of carbonsuboxide C3O2, which in turn was synthesized from malonic acid bis(trimethylsilylester). Two different 13C labeling schemes were applied to probe inter- and intramonomeric bonds in the polymer by dipolar solid-state NMR methods and also to allow quantitative 13C MAS NMR spectra. Four types of carbon environments can be distinguished in the NMR spectra. Double-quantum and triple-quantum 2D correlation experiments were used to assign the observed peaks using the through-space and through-bond dipolar coupling. In order to obtain distance constraints for the intermonomeric bonds, double-quantum constant-time experiments were performed. In these experiments an additional filter step was applied to suppress contributions from not directly bonded 13C,13C spin pairs. The 13C NMR intensities, chemical shifts, connectivities and distances gave constraints for both the polymerization mechanism and the short-range order of the polymer. The experimental results were complemented by bond lengths predicted by density functional theory methods for several previously suggested models. Based on the presented evidence we can unambiguously exclude models based on gamma-pyronic units and support models based on alpha-pyronic units. The possibility of planar ladder- and bracelet-like alpha-pyronic structures is discussed.

Exploring chemical diversity of α-pyrone antibiotics: molecular basis of myxopyronin biosynthesis.

PubMed

Sucipto, Hilda; Wenzel, Silke C; Müller, Rolf

2013-09-02

Myxopyronins and corallopyronins are structurally related α-pyrone antibiotics from myxobacteria. They are thought to represent a highly promising compound class for the development of broad-spectrum antibacterial therapeutic agents, because of their ability to inhibit RNA polymerase through interaction with the "switch region", a recently identified novel drug target. Here we describe the identification and characterization of the myxopyronin biosynthetic pathway from Myxococcus fulvus Mx f50. A detailed comparison with the recently identified corallopyronin biosynthetic pathway revealed the genetic and biochemical basis, thus explaining the observed structural differences between the two natural product families. Directed mutagenesis procedures for M. fulvus Mx f50 were developed to enable functional studies and pathway modifications. Our work provided new insights into myxopyronin biosynthesis and led to the production of a novel and unexpected myxopyronin derivative. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Production of 6-pentyl-α-pyrone by trichoderma harzianum in solid-state fermentation

PubMed Central

de Souza Ramos, Aline; Fiaux, Sorele Batista; Leite, Selma Gomes Ferreira

2008-01-01

Many Trichoderma species are able to produce 6-pentyl-α-pyrone (6-PP), a lactone with coconut-like aroma. In the present work, several culture parameters were studied to enhance the production of 6-PP by Trichoderma harzianum 4040 in solid-state fermentation. Green coir powder added to a nutrient solution was used as support material for fermentation. A Plackett-Burman screening technique was applied, followed by a fractionary factorial design. The best culture conditions within the experimental domain studied were (100 g support)−1: sucrose, 3 g; NaNO3, 0.24 g; (NH4)2SO4, 0.18 g; KH2PO4, 0.1 g; inoculum concentration, 2.2 × 106 spores; moisture level, 55%. The temperature established was 28°C. The fermentation under the selected conditions led to a 6-PP production six times higher (5.0 mg/g dry matter) than the initial one (0.8 mg/g dry matter) after seven days of cultivation. PMID:24031295

Production of 6-pentyl-α-pyrone by trichoderma harzianum in solid-state fermentation.

PubMed

de Souza Ramos, Aline; Fiaux, Sorele Batista; Leite, Selma Gomes Ferreira

2008-10-01

Many Trichoderma species are able to produce 6-pentyl-α-pyrone (6-PP), a lactone with coconut-like aroma. In the present work, several culture parameters were studied to enhance the production of 6-PP by Trichoderma harzianum 4040 in solid-state fermentation. Green coir powder added to a nutrient solution was used as support material for fermentation. A Plackett-Burman screening technique was applied, followed by a fractionary factorial design. The best culture conditions within the experimental domain studied were (100 g support)(-1): sucrose, 3 g; NaNO3, 0.24 g; (NH4)2SO4, 0.18 g; KH2PO4, 0.1 g; inoculum concentration, 2.2 × 10(6) spores; moisture level, 55%. The temperature established was 28°C. The fermentation under the selected conditions led to a 6-PP production six times higher (5.0 mg/g dry matter) than the initial one (0.8 mg/g dry matter) after seven days of cultivation.

Integrated Metabolomics and Morphogenesis Reveal Volatile Signaling of the Nematode-Trapping Fungus Arthrobotrys oligospora.

PubMed

Wang, Bai-Le; Chen, Yong-Hong; He, Jia-Ning; Xue, Hua-Xi; Yan, Ni; Zeng, Zhi-Jun; Bennett, Joan W; Zhang, Ke-Qin; Niu, Xue-Mei

2018-05-01

The adjustment of metabolic patterns is fundamental to fungal biology and plays vital roles in adaptation to diverse ecological challenges. Nematode-trapping fungi can switch their lifestyle from saprophytic to pathogenic by developing specific trapping devices induced by nematodes to infect their prey as a response to nutrient depletion in nature. However, the chemical identity of the specific fungal metabolites used during the switch remains poorly understood. We hypothesized that these important signal molecules might be volatile in nature. Gas chromatography-mass spectrometry was used to carry out comparative analysis of fungal metabolomics during the saprophytic and pathogenic lifestyles of the model species Arthrobotrys oligospora Two media commonly used in research on this species, cornmeal agar (CMA) and potato dextrose agar (PDA), were chosen for use in this study. The fungus produced a small group of volatile furanone and pyrone metabolites that were associated with the switch from the saprophytic to the pathogenic stage. A. oligospora fungi grown on CMA tended to produce more traps and employ attractive furanones to improve the utilization of traps, while fungi grown on PDA developed fewer traps and used nematode-toxic furanone metabolites to compensate for insufficient traps. Another volatile pyrone metabolite, maltol, was identified as a morphological regulator for enhancing trap formation. Deletion of the gene AOL_s00079g496 in A. oligospora led to increased amounts of the furanone attractant (2-fold) in mutants and enhanced the attractive activity (1.5-fold) of the fungus, while it resulted in decreased trap formation. This investigation provides new insights regarding the comprehensive tactics of fungal adaptation to environmental stress, integrating both morphological and metabolomic mechanisms. IMPORTANCE Nematode-trapping fungi are a unique group of soil-living fungi that can switch from the saprophytic to the pathogenic lifestyle once they come into contact with nematodes as a response to nutrient depletion. In this study, we investigated the metabolic response during the switch and the key types of metabolites involved in the interaction between fungi and nematodes. Our findings indicate that A. oligospora develops multiple and flexible metabolic tactics corresponding to different morphological responses to nematodes. A. oligospora can use similar volatile furanone and pyrone metabolites with different ecological functions to help capture nematodes in the fungal switch from the saprophytic to the pathogenic lifestyle. Furthermore, studies with A. oligospora mutants with increased furanone and pyrone metabolites confirmed the results. This investigation reveals the importance of volatile signaling in the comprehensive tactics used by nematode-trapping fungi, integrating both morphological and metabolomic mechanisms. Copyright © 2018 Wang et al.

Integrated Metabolomics and Morphogenesis Reveal Volatile Signaling of the Nematode-Trapping Fungus Arthrobotrys oligospora

PubMed Central

Wang, Bai-Le; Chen, Yong-Hong; He, Jia-Ning; Xue, Hua-Xi; Yan, Ni; Zeng, Zhi-Jun; Bennett, Joan W.

2018-01-01

ABSTRACT The adjustment of metabolic patterns is fundamental to fungal biology and plays vital roles in adaptation to diverse ecological challenges. Nematode-trapping fungi can switch their lifestyle from saprophytic to pathogenic by developing specific trapping devices induced by nematodes to infect their prey as a response to nutrient depletion in nature. However, the chemical identity of the specific fungal metabolites used during the switch remains poorly understood. We hypothesized that these important signal molecules might be volatile in nature. Gas chromatography-mass spectrometry was used to carry out comparative analysis of fungal metabolomics during the saprophytic and pathogenic lifestyles of the model species Arthrobotrys oligospora. Two media commonly used in research on this species, cornmeal agar (CMA) and potato dextrose agar (PDA), were chosen for use in this study. The fungus produced a small group of volatile furanone and pyrone metabolites that were associated with the switch from the saprophytic to the pathogenic stage. A. oligospora fungi grown on CMA tended to produce more traps and employ attractive furanones to improve the utilization of traps, while fungi grown on PDA developed fewer traps and used nematode-toxic furanone metabolites to compensate for insufficient traps. Another volatile pyrone metabolite, maltol, was identified as a morphological regulator for enhancing trap formation. Deletion of the gene AOL_s00079g496 in A. oligospora led to increased amounts of the furanone attractant (2-fold) in mutants and enhanced the attractive activity (1.5-fold) of the fungus, while it resulted in decreased trap formation. This investigation provides new insights regarding the comprehensive tactics of fungal adaptation to environmental stress, integrating both morphological and metabolomic mechanisms. IMPORTANCE Nematode-trapping fungi are a unique group of soil-living fungi that can switch from the saprophytic to the pathogenic lifestyle once they come into contact with nematodes as a response to nutrient depletion. In this study, we investigated the metabolic response during the switch and the key types of metabolites involved in the interaction between fungi and nematodes. Our findings indicate that A. oligospora develops multiple and flexible metabolic tactics corresponding to different morphological responses to nematodes. A. oligospora can use similar volatile furanone and pyrone metabolites with different ecological functions to help capture nematodes in the fungal switch from the saprophytic to the pathogenic lifestyle. Furthermore, studies with A. oligospora mutants with increased furanone and pyrone metabolites confirmed the results. This investigation reveals the importance of volatile signaling in the comprehensive tactics used by nematode-trapping fungi, integrating both morphological and metabolomic mechanisms. PMID:29453265

Triacetic acid lactone production in industrial Saccharomyces yeast strains

USDA-ARS?s Scientific Manuscript database

Triacetic acid lactone (TAL) is a potential platform chemical that can be produced in yeast. To evaluate the potential for industrial yeast strains to produce TAL, the g2ps1 gene encoding 2-pyrone synthase was transformed into thirteen industrial yeast strains of varied genetic background. TAL produ...

Triacetic acid lactone production from Saccharomyces cerevisiae

USDA-ARS?s Scientific Manuscript database

Triacetic acid lactone (TAL) is a potential platform chemical produced from acetyl-CoA and malonyl-CoA by the Gerbera hybrida 2-pyrone synthase (2PS) gene. Studies are ongoing to optimize production, purification, and chemical modification of TAL, which can be used to create the commercial chemicals...

Polyketides from Pestalotiopsis zonata and structure revision of pestalrones A and B.

PubMed

Xu, Xin; Liu, Chang; Dong, Ya-Jing; Liu, Fang-Ru; Xu, Xiu-Mei; Li, De-Sheng; Li, Dan-Yi; Li, Zhan-Lin

2017-11-23

The structures of pestalrones A-B were revised via reinterpretation of the NMR data and a brief chemical transformation from the co-occurring polyketides, in our investigation on the secondary metabolites of Pestalotiopsis zonata, which also afforded a new α-pyrone derivative, pestazonatic acid, and four known analogs.

Tin(IV) chloride catalyzed cycloaddition reactions between 3-ethoxycyclobutanones and allylsilanes.

PubMed

Matsuo, Jun-ichi; Sasaki, Shun; Hoshikawa, Takaya; Ishibashi, Hiroyuki

2009-09-03

Formal [4 + 2] cycloaddition between various 3-ethoxycyclobutanones and allyltrialkylsilanes proceeded to give 3-ethoxy-5-[(trialkylsilyl)methyl]cyclohexan-1-ones by catalysis with tin(VI) chloride. The use of allyl-tert-butyldiphenylsilane induced 1,5-hydride transfer, which gave 2-[3-(tert-butyldiphenylsilyl)propyl]-6-methyltetrahydro-4-pyrones.

Asperpyrone-Type Bis-Naphtho-γ-Pyrones with COX-2-Inhibitory Activities from Marine-Derived Fungus Aspergillus niger.

PubMed

Fang, Wei; Lin, Xiuping; Wang, Jianjiao; Liu, Yonghong; Tao, Huaming; Zhou, Xuefeng

2016-07-20

Bis-naphtho-γ-pyrones (BNPs) are an important group of aromatic polyketides derived from fungi, and asperpyrone-type BNPs are produced primarily by Aspergillus species. The fungal strain Aspergillus niger SCSIO Jcsw6F30, isolated from a marine alga, Sargassum sp., and identified according to its morphological traits and the internal transcribed spacer (ITS) region sequence, was studied for BNPs secondary metabolisms. After HPLC/MS analysis of crude extract of the fermentation broth, 11 asperpyrone-type BNPs were obtained directly and quickly by chromatographic separation in the extract, and those isolated asperpyrone-type BNPs were structurally identified by NMR and MS analyses. All of the BNPs showed weak cytotoxicities against 10 human tumor cells (IC50 > 30 μM). However, three of them, aurasperone F (3), aurasperone C (6) and asperpyrone A (8), exhibited obvious COX-2-inhibitory activities, with the IC50 values being 11.1, 4.2, and 6.4 μM, respectively. This is the first time the COX-2-inhibitory activities of BNPs have been reported.

Heat Stable Polymers: Polyphenylene and Other Aromatic Polymers

DTIC Science & Technology

1977-01-01

crystalline transition temperature . Model reactions on 4- and 6-phienyl-2-pyrones show that this monomer type is unsuitable for the syntheses of... temperature to a rod-like molecule with a high glass transition temperature . The polymerization reaction is acid catalyzed, but is carried out most...Polymerization Reactions...................24 Solution Properties......................27 Phase Transition Temperatures , Thermal Stability and Thermomechanical

Co-immobilized Coupled Enzyme Systems in Biotechnology

DTIC Science & Technology

2010-01-01

Dongen et a /. , A three-enzyme cascade reaction through positional assembly of enzymes in a polymersome nanoreactor. Chemistry -A European Journal...coupled to a second immobilized peroxidase reac- tor, for example, produces a variety of flavonoids and pyrone derivatives (Kim et al., 2009...Lipase-catalyzed regioselective one-step synthesis of penta-O-acetyl-3-hydroxylactal. Europeall Joumal of Organic Chemistry , 2009(20): 3327-3329

Synthesis and biological evaluation of matrine derivatives containing benzo-α-pyrone structure as potent anti-lung cancer agents

PubMed Central

Wu, Lichuan; Wang, Guizhen; Liu, Shuaibing; Wei, Jinrui; Zhang, Sen; Li, Ming; Zhou, Guangbiao; Wang, Lisheng

2016-01-01

Matrine, an active component of root extracts from Sophora flavescens Ait, is the main chemical ingredient of Fufang Kushen injection which was approved by Chinese FDA (CFDA) in 1995 as an anticancer drug to treat non-small cell lung cancer and liver cancer in combination with other anticancer drugs. Owning to its druggable potential, matrine is considered as an ideal lead compound for modification. We delineate herein the synthesis and anticancer effects of 17 matrine derivatives bearing benzo-α-pyrone structures. The results of cell viability assays indicated that most of the target compounds showed improved anticancer effects. Further studies showed that compound 5i could potently inhibit lung cancer cell proliferation in vitro and in vivo with no obvious side effects. Moreover, compound 5i could induce G1 cell cycle arrest and autophagy in lung cancer cells through up-regulating P27, down-regulating CDK4 and cyclinD1 and attenuating PI3K/Akt/mTOR pathway. Suppression of autophagy attenuated 5i induced proliferation inhibition. Collectively, our results infer that matrine derivative 5i bears therapeutic potentials for lung cancer. PMID:27786281

Single step synthesis of strigolactone analogues from cyclic keto enols, germination stimulants for seeds of parasitic weeds.

PubMed

Mwakaboko, Alinanuswe S; Zwanenburg, Binne

2011-08-15

The single step synthesis of a newly designed series of strigolactones (SLs) from cyclic keto enols is described. The germinating activity of these SL analogues towards seeds of the parasitic weeds Striga and Orobanche spp. is reported. The first of these SL analogues are derived from the hydroxyl γ-pyrones kojic acid and maltol, the second type from hydroxyl α-pyrones, namely, 4-hydroxy-6-methyl-2H-pyran-2-one and 4-hydroxy-coumarin and the third type from 1,3-diketones, namely, 1,3-cyclohexane-dione (dimedone) and tricyclic 1,3-dione. All keto enols are coupled in a single step with the appropriate D-ring precursor in the presence of a base to give the desired SL analogues. All SL analogues are acceptably biologically active in inducing the germination of seeds of Striga hermonthica and Orobanchecernua. Most interesting are the analogues derived from 4-hydroxy coumarin and dimedone, as they have a remarkably high biological activity towards the seeds of parasitic weeds at relatively low concentrations, comparable with that of the general standard stimulant GR24. Copyright © 2011 Elsevier Ltd. All rights reserved.

Sinensetin attenuates LPS-induced inflammation by regulating the protein level of IκB-α.

PubMed

Shin, Hye-Sun; Kang, Seong-Il; Yoon, Seon-A; Ko, Hee-Chul; Kim, Se-Jae

2012-01-01

Sinensetin is one of the polymethoxyflavones (PMFs) having five methoxy groups on the basic benzo-γ-pyrone skeleton with a carbonyl group at the C(4) position. We investigated in this study the anti-inflammatory activity of sinensetin in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Sinensetin showed anti-inflammatory activity by regulating the protein level of inhibitor κB-α (IκB-α).

A revision and key for the tribe Diaphorolepidini (Serpentes: Dipsadidae) and checklist for the genus Synophis.

PubMed

Pyron, R Alexander; Arteaga, Alejandro; Echevarría, Lourdes Y; Torres-Carvajal, Omar

2016-09-28

The genus Synophis contains a number of enigmatic species, distributed primarily in the Andean highlands of northern South America. Their extreme crypsis and rarity has precluded detailed study of most species. A recent flurry of collection activity resulted in the accession of many new specimens, and the description of 4 new species in 2015, doubling the number of described taxa. However, lingering questions remain regarding the assignment of many new and historical specimens, the morphological limits and geographical ranges of the species, and their phylogenetic relationships. We analyze new and existing morphological and molecular data to produce a new molecular phylogeny and revised morphological descriptions. We validate the previously unavailable tribe name Diaphorolepidini Jenner, Pyron, Arteaga, Echevarría, & Torres-Carvajal tribe nov., describe a 9th species Synophis niceforomariae Pyron, Arteaga, Echevarría, & Torres-Carvajal sp. nov., and offer new Standard Names in English and Spanish for the group: Andean Shadow Snakes and Culebras Andinas de la Sombra, respectively. A variety of features such as vertebrae and hemipenes show an interesting range of variation in the group, which should be evaluated in future studies, to refine species limits and diagnoses further. Cryptic and undiscovered diversity undoubtedly remains, and we hope this summary provides a robust basis for future work.

Dianthosaponins A-F, triterpene saponins, flavonoid glycoside, aromatic amide glucoside and γ-pyrone glucoside from Dianthus japonicus.

PubMed

Nakano, Takahiro; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki

2011-01-01

From aerial parts of Dianthus japonicus, six new and seven known oleanane-type triterpene saponins were isolated. The structures of the new saponins, named dianthosaponins A-F, were elucidated by means of high resolution mass spectrometry, and extensive inspection of one- and two-dimensional NMR spectroscopic data. A new C-glycosyl flavone, a glycosidic derivative of anthranilic acid amide and a maltol glucoside were also isolated.

Selective C-O Hydrogenolysis and Decarboxylation of Biomass-Derived Heterocyclic Compounds over Heterogeneous Catalysts

NASA Astrophysics Data System (ADS)

Chia, Mei

The catalytic deoxygenation of biomass-derived compounds through selective C-O hydrogenolysis, catalytic transfer hydrogenation and lactonization, and decarboxylation to value-added chemicals over heterogeneous catalysts was examined under liquid phase reaction conditions. The reactions studied involve the conversion or production of heterocyclic compounds, specifically, cyclic ethers, lactones, and 2-pyrones. A bimetallic RhRe/C catalyst was found to be selective for the hydrogenolysis of secondary C-O bonds for a broad range cyclic ethers and polyols. Results from experimentally-observed reactivity trends, NH3 temperature-programmed desorption, fructose dehydration reaction studies, and first-principles density functional theory (DFT) calculations are consistent with the hypothesis of a bifunctional catalyst which facilitates acid-catalyzed ring-opening and dehydration coupled with metal-catalyzed hydrogenation. C-O hydrogenolysis and fructose dehydration activities were observed to decrease with an increase in reduction temperature and a decrease in the number of surface metallic Re atoms measured by in situ X-ray absorption spectroscopy. No C-O hydrogenolysis activity was detected over RhRe/C under water-free conditions. The activation of water molecules by Re atoms on the surface of metallic Rh is suggested to result in the formation of Bronsted acidity over RhRe/C. The catalytic transfer hydrogenation and lactonization of levulinic acid and its esters to gamma-valerolactone was accomplished through the Meerwein-Ponndorf-Verley reaction over metal oxide catalysts using secondary alcohols as the hydrogen donor. ZrO2 was a highly active material for CTH under batch and continuous flow reaction conditions; the initial activity of the catalyst was repeatedly regenerable by calcination in air, with no observable loss in catalytic activity. Lastly, the 2-pyrone, triacetic acid lactone, is shown to be a promising biorenewable platform chemical from which a wide range of chemical intermediates and end products can be obtained using heterogeneous catalysts or by thermal decomposition. Mechanistic insights from experimentally-observed reactivity trends and results from DFT calculations indicate that 2-pyrones undergo reactions unique to their structure such as keto-enol tautomerization, retro Diels-Alder, and nucleophilic attack by water. Ring-opening and decarboxylation reactions were found to be governed by key structural features such as the degree of saturation in the ring (e.g., C4=C5 bond), nature of the solvent, and presence of an acid catalyst.

Modiolide and pyrone derivatives from the sea fan-derived fungus Curvularia sp. PSU-F22.

PubMed

Trisuwan, Kongkiat; Rukachaisirikul, Vatcharin; Phongpaichit, Souwalak; Preedanon, Sita; Sakayaroj, Jariya

2011-05-01

Investigation of secondary metabolites from the sea fan-derived fungus Curvularia sp. PSU-F22 resulted in isolation of three new metabolites, curvulapyrone (1), curvulalide (2) and curvulalic acid (3) together with six known compounds, modiolides A (4) and B (5), pyrenolide A (6), stagonolide E (7), mycoepoxydiene (8), and deacetylmycoepoxydiene (9). Their antimicrobial activity against Staphylococcus aureus ATCC 25923, methicillin-resistant S. aureus and Microsporum gypseum SH-MU-4 were examined.

Penicyrones A and B, an epimeric pair of α-pyrone-type polyketides produced by the marine-derived Penicillium sp.

PubMed

Bu, Ying-Yue; Yamazaki, Hiroyuki; Takahashi, Ohgi; Kirikoshi, Ryota; Ukai, Kazuyo; Namikoshi, Michio

2016-01-01

Two polyketides containing an α-pyrone unit, named penicyrones A (1) and B (2), were isolated from a culture broth of the marine-derived Penicillium sp. TPU1271 together with nine known compounds: verrucosidin (3), fructigenine A (4), verrucofortine (5), cyclo-(L-Trp-L-Phe) (6), cyclopenol (7), cyclopenin (8), penipratynolene (9), aspterric acid (10) and viridicatol (11). The structures of 1 and 2 were elucidated by analyzing the spectroscopic data of 1, 2 and their O-acetyl derivatives (1a and 2a). Compounds 1 and 2 were epimers of each other at the C-9 position. The absolute configurations of 1 and 2 were assigned on the basis of NOESY data for 1, 2, 1a and 2a, a conformational analysis and the identity of the biogenetic pathway with verrucosidin (3). The planar structure of penicyrones was found in the SciFinder as a compound in the commercial chemical libraries; however, the stereostructure and spectroscopic data were not available. Therefore, this is the first study on the isolation and structure elucidation, including the absolute configurations, of penicyrones A (1) and B (2) as fungal metabolites. Compound 3 exhibited growth inhibitory activity against Mycobacterium smegmatis at 40 μg per disc (inhibition zone of 11 mm). This is the first study to demonstrate that verrucosidin (3) exhibited anti-mycobacterial activity.

New insights into the antioxidant activity and cytotoxicity of arzanol and effect of methylation on its biological properties.

PubMed

Rosa, Antonella; Atzeri, Angela; Nieddu, Mariella; Appendino, Giovanni

2017-06-01

The heterodimeric phloroglucinyl pyrone arzanol (Arz) has raised considerable interest because of its antiviral, anti-inflammatory, and antioxidant activity. We have investigated the effect of methylation of the pyrone moiety on the antioxidant activity and cytotoxicity of Arz. This manoeuvre, that left the polyphenolic moiety unscathed, was nevertheless detrimental for antioxidant activity in both the cholesterol thermal degradation- and the Cu 2+ -induced liposome oxidation assays, providing evidence of structure-activity relationships that go beyond the preservation of the polyphenolic pharmacophore. The antioxidant activity of Arz was retained also in the Fe-NTA model of in vivo oxidative stress, with protective effect on the oxidative degradation of plasmatic lipids, unsaturated fatty acids and cholesterol. Both Arz and methylarzanol (Me-Arz) were devoid of toxic effect on colonic differentiated Caco-2 cells up to 100μM, but significantly reduced cancer Caco-2 cell viability at lower dosages. Arz could also selectively reduce viability of other cancer cell lines, [murine melanoma cells (B16F10 cells), human cervical carcinoma cells (HeLa cells)], suggesting that it can act as a selective modulator of cell processes typical of cancer cells. Taken together, our results qualify Arz as a lead structure for further in vivo investigation of its pharmacological potential. Copyright © 2017 Elsevier B.V. All rights reserved.

Whole-genome sequencing of Aspergillus tubingensis G131 and overview of its secondary metabolism potential.

PubMed

Choque, Elodie; Klopp, Christophe; Valiere, Sophie; Raynal, José; Mathieu, Florence

2018-03-15

Black Aspergilli represent one of the most important fungal resources of primary and secondary metabolites for biotechnological industry. Having several black Aspergilli sequenced genomes should allow targeting the production of certain metabolites with bioactive properties. In this study, we report the draft genome of a black Aspergilli, A. tubingensis G131, isolated from a French Mediterranean vineyard. This 35 Mb genome includes 10,994 predicted genes. A genomic-based discovery identifies 80 secondary metabolites biosynthetic gene clusters. Genomic sequences of these clusters were blasted on 3 chosen black Aspergilli genomes: A. tubingensis CBS 134.48, A. niger CBS 513.88 and A. kawachii IFO 4308. This comparison highlights different levels of clusters conservation between the four strains. It also allows identifying seven unique clusters in A. tubingensis G131. Moreover, the putative secondary metabolites clusters for asperazine and naphtho-gamma-pyrones production were proposed based on this genomic analysis. Key biosynthetic genes required for the production of 2 mycotoxins, ochratoxin A and fumonisin, are absent from this draft genome. Even if intergenic sequences of these mycotoxins biosynthetic pathways are present, this could not lead to the production of those mycotoxins by A. tubingensis G131. Functional and bioinformatics analyses of A. tubingensis G131 genome highlight its potential for metabolites production in particular for TAN-1612, asperazine and naphtho-gamma-pyrones presenting antioxidant, anticancer or antibiotic properties.

Inhibition of Alzheimer’s Amyloid Toxicity with a Tricyclic Pyrone Molecule In Vitro and In Vivo

PubMed Central

Hong, Hyun-Seok; Rana, Sandeep; Barrigan, Lydia; Shi, Aibin; Zhang, Yi; Zhou, Feimeng; Jin, Lee-Way; Hua, Duy H.

2009-01-01

Small amyloid β 1–42 aggregates are toxic to neurons and may be the primary toxic species in Alzheimer’s disease (AD). Methods to reduce the level of Aβ, prevent Aβ aggregation, and eliminate existing Aβ aggregates have been proposed for treatment of AD. A tricyclic pyrone named CP2 is found to prevent cell death associated with Aβ oligomers. We studied the possible mechanisms of neuroprotection by CP2. Surface plasmon resonance spectroscopy shows a direct binding of CP2 with Aβ42 oligomer. Circular dichroism spectroscopy reveals monomeric Aβ42 peptide remains as a random coil/α-helix structure in the presence of CP2 over 48 h. Atomic force microscopy (AFM) studies show CP2 exhibits similar ability to inhibit Aβ42 aggregation as that of Congo Red and curcumin. AFM closed-fluid cell study demonstrates that CP2 disaggregates Aβ42 oligomers and protofibrils. CP2 also blocks Aβ fibrillations using a protein quantification method. Treatment of 5x FAD mice, a robust Aβ42-producing animal model of AD, with a two-week course of CP2 resulted in 40% and 50% decreases in non-fibrillar and fibrillar Aβ species, respectively. Our results suggest that CP2 might be beneficial to AD patients by preventing Aβ aggregation and disaggregating existing Aβ oligomers and protofibrils. PMID:19141069

Vibrational spectroscopic study of dehydroacetic acid and its cinnamoyl pyrone derivatives

NASA Astrophysics Data System (ADS)

Billes, Ferenc; Elečková, Lenka; Mikosch, Hans; Andruch, Vasil

2015-07-01

The infrared and Raman spectra of dehydroacetic acid and some of its derivatives were measured. The assignments of the vibrational bands were based on quantum chemical calculations and normal coordinate analysis. The optimized structures, atomic net charges and dipole moments of the investigated molecules were also results of our quantum chemical calculations. The analysis of the last properties made possible a deeper insight into the structure and substituent effect on the investigated molecules. One of them is presented in the graphical abstract.

Biosynthesis and Total Synthesis of Pyrronazol B: a Secondary Metabolite from Nannocystis pusilla.

PubMed

Witte, Swjatoslaw N R; Hug, Joachim J; Géraldy, Magalie N E; Müller, Rolf; Kalesse, Markus

2017-11-13

The first stereoselective total synthesis of the natural product pyrronazol B, which contains a chlorinated pyrrole-oxazole-pyrone framework, has been achieved. Genome sequencing of the myxobacterial producer strain Nannocystis pusilla Ari7 led to the identification of the putative biosynthetic gene cluster. The proposed biosynthetic pathway was supported by feeding experiments with stable isotopes of three biosynthetic building blocks, namely l-proline, l-serine, and l-methionine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Two novel isocoumarins from Erigeron breviscapus].

PubMed

Li, Jing; Yu, De-Quan

2013-07-01

Two novel isocoumarins, erigeronone C (1) and D (2), were isolated from the ethanol extract of the whole plant of Erigeron breviscapus (Vant.) Hand.-Mazz (Compositae). Their structures were respectively elucidated as 8, 9-dihydroxypyrano [3, 2-c] isochromen-4, 6-dione (1) and 4, 7-dihydroxy-3-(3-hydroxy-4-oxo-4H-pyran-2-yl)-1H-isochromen-1-one (2) on the basis of spectral analyses. Both structures of 1 and 2 possess a gamma-pyrone moiety and that is rare in natural products.

Bifurcation analysis of the regulation of nociceptive neuronal activity

NASA Astrophysics Data System (ADS)

Dik, O. E.

2017-11-01

A model of the membrane of a nociceptive neuron from a rat dorsal ganglion has been used to address the problem of analyzing the regulation of nociceptive signals by 5-hydroxy-γ-pyrone-2-carboxylic acid, which is the active pharmaceutic ingredient of the analgesic Anoceptin. The study has applied bifurcation analysis to report the relationship between the values of model parameters and the type of problem solution before and after the parameters change in response to analgesic modulation.

Kalkipyrone B, a marine cyanobacterial γ-pyrone possessing cytotoxic and anti-fungal activities

PubMed Central

Bertin, Matthew J; Demirkiran, Ozlem; Navarro, Gabriel; Moss, Nathan A; Lee, John; Goldgof, Gregory M; Vigil, Edgar; Winzeler, Elizabeth A; Valeriote, Fred A; Gerwick, William H

2015-01-01

Bioassay-guided fractionation of two marine cyanobacterial extracts using the H-460 human lung cancer cell line and the OVC-5 human ovarian cancer cell line led to the isolation of three related α-methoxy-β, β’-dimethyl-γ-pyrones each containing a modified alkyl chain, one of which was identified as the previously reported kalkipyrone and designated kalkipyrone A. The second compound was an analog designated kalkipyrone B. The third was identified as the recently reported yoshipyrone A, also isolated from a marine cyanobacterium. Kalkipyrone A and B were obtained from a field-collection of the cyanobacterium Leptolyngbya sp. from Fagasa Bay, American Samoa, while yoshipyrone A was isolated from a field-collection of cyanobacteria (cf. Schizothrix sp.) from Panama. One-dimensional and two-dimensional NMR experiments were used to determine the overall structures and relative configurations of the kalkipyrones, and the absolute configuration of kalkipyrone B was determined by 1H NMR analysis of diastereomeric Mosher’s esters. Kalkipyrone A showed good cytotoxicity to H-460 human lung cancer cells (EC50 = 0.9 µM), w M), while kalkipyrone B and yoshipyrone A were less active (EC50 = 9.0 µM and > 10 µM, respectively). Both kalkipyrone A and B showed moderate toxicity to Saccharomyces cerevisiae ABC16-Monster strain (IC50 = 14.6 and 13.4 µM, respectively), whereas yoshipyrone A was of low toxicity to this yeast strain (IC50 = 63.8 µM). PMID:26632528

EncM, a versatile enterocin biosynthetic enzyme involved in Favorskii oxidative rearrangement, aldol condensation, and heterocycle-forming reactions

PubMed Central

Xiang, Longkuan; Kalaitzis, John A.; Moore, Bradley S.

2004-01-01

The bacteriostatic natural product enterocin from the marine microbe “Streptomyces maritimus” has an unprecedented carbon skeleton that is derived from an aromatic polyketide biosynthetic pathway. Its caged tricyclic, nonaromatic core is derived from a linear poly-β-ketide precursor that formally undergoes a Favorskii-like oxidative rearrangement. In vivo characterization of the gene encM through mutagenesis and heterologous biosynthesis demonstrated that its protein product not only is solely responsible for the oxidative C—C rearrangement, but also facilitates two aldol condensations plus two heterocycle forming reactions. In total, at least five chiral centers and four rings are generated by this multifaceted flavoprotein. Heterologous expression of the enterocin biosynthesis genes encABCDLMN in Streptomyces lividans resulted in the formation of the rearranged metabolite desmethyl-5-deoxyenterocin and the shunt products wailupemycins D-G. Addition of the methyltransferase gene encK, which was previously proposed through mutagenesis to additionally assist EncM in the Favorskii rearrangement, shifted the production to the O-methyl derivative 5-deoxyenterocin. The O-methyltransferase EncK seems to be specific for the pyrone ring of enterocin, because bicyclic polyketides bearing pyrone rings are not methylated in vivo. Expression of encM with different combinations of homologous actinorhodin biosynthesis genes did not result in the production of oxidatively rearranged enterocin-actinorhodin hybrid compounds as anticipated, suggesting that wild-type EncM may be specific for its endogenous type II polyketide synthase or for benzoyl-primed polyketide precursors. PMID:15505225

Application of microalgae hydrolysate as a fermentation medium for microbial production of 2-pyrone 4,6-dicarboxylic acid.

PubMed

Htet, April N; Noguchi, Mana; Ninomiya, Kazuaki; Tsuge, Yota; Kuroda, Kosuke; Kajita, Shinya; Masai, Eiji; Katayama, Yoshihiro; Shikinaka, Kazuhiro; Otsuka, Yuichiro; Nakamura, Masaya; Honda, Ryo; Takahashi, Kenji

2018-06-01

Actual biomass of microalgae was tested as a fermentation substrate for microbial production of 2-pyrone 4,6-dicarboxylic acid (PDC). Acid-hydrolyzed green microalgae Chlorella emersonii (algae hydrolysate) was diluted to adjust the glucose concentration to 2 g/L and supplemented with the nutrients of Luria-Bertani (LB) medium (tryptone 10 g/L and yeast extract 5 g/L). When the algae hydrolysate was used as a fermentation source for recombinant Escherichia coli producing PDC, 0.43 g/L PDC was produced with a yield of 20.1% (mol PDC/mol glucose), whereas 0.19 g/L PDC was produced with a yield of 8.6% when LB medium supplemented with glucose was used. To evaluate the potential of algae hydrolysate alone as a fermentation medium for E. coli growth and PDC production, the nutrients of LB medium were reduced from the algae hydrolysate medium. Interestingly, 0.17 g/L PDC was produced even without additional nutrient, which was comparable to the case using pure glucose medium with nutrients of LB medium. When using a high concentration of hydrolysate without additional nutrients, 1.22 g/L PDC was produced after a 24-h cultivation with the yield of 16.1%. Overall, C. emersonii has high potential as cost-effective fermentation substrate for the microbial production of PDC. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

The anxiolytic-like effect of 6-styryl-2-pyrone in mice involves GABAergic mechanism of action.

PubMed

Chaves, Edna Maria Camelo; Honório-Júnior, Jose Eduardo Ribeiro; Sousa, Caren Nádia Soares; Monteiro, Valdécio Silveira; Nonato, Dayanne Terra Tenório; Dantas, Leonardo Pimentel; Lúcio, Ana Silvia Suassuna Carneiro; Barbosa-Filho, José Maria; Patrocínio, Manoel Cláudio Azevedo; Viana, Glauce Socorro Barros; Vasconcelos, Silvânia Maria Mendes

2018-02-01

The present work aims to investigate the anxiolytic activity of 6-styryl-2-pyrone (STY), obtained from Aniba panurensis, in behavioral tests and amino acids dosage on male Swiss mice. The animals were treated with STY (1, 10 or 20 mg), diazepam (DZP 1 or 2 mg/kg) or imipramine (IMI 30 mg/kg). Some groups were administered with flumazenil, 30 min before administration of the STYor DZP. The behavioral tests performed were open field, rota rod, elevated plus maze (EPM), hole-board (HB) and tail suspension test (TST). After behavioral tests, these animals were sacrificed and had their prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) dissected for assaying amino acids (aspartate- ASP, glutamate- GLU, glycine- GLY, taurine- TAU and Gamma-aminobutyric acid- GABA). In EPM test, STY or DZP increased the number of entries and the time of permanence in the open arms, but these effects were reverted by flumazenil. In the HB test, STY increased the number of head dips however this effect was blocked by flumazenil. The effects of the STY on amino acid concentration in PFC showed increased GLU, GABA and TAU concentrations. In hippocampus, STY increased the concentrations of all amino acids studied. In striatum, STY administration at lowest dose reduced GLU concentrations, while the highest dosage caused the opposite effect. GLI, TAU and GABA concentrations increased with STY administration at highest doses. In conclusion, this study showed that STY presents an anxiolytic-like effect in behavioral tests that probably is related to GABAergic mechanism of action.

Chip-based polyketide biosynthesis and functionalization.

PubMed

Ku, Bosung; Cha, Junhoe; Srinivasan, Aravind; Kwon, Seok Joon; Jeong, Jae-Choel; Sherman, David H; Dordick, Jonathan S

2006-01-01

We demonstrate construction and novel compound synthesis from a synthetic metabolic pathway consisting of a type III polyketide synthase (PKS) known as 1,3,6,8-tetrahydroxynaphthalene synthase (THNS) from Streptomyces coelicolor and soybean peroxidase (SBP) in a microfluidic platform. THNS immobilized to Ni-NTA agarose beads is prepacked into a microfluidic channel, while SBP is covalently attached to the walls of a second microfluidic channel precoated with a reactive poly(maleic anhydride) derivative. The result is a tandem, two-step biochip that enables the synthesis of novel polyketide derivatives. The first microchannel, consisting of THNS, results in the conversion of malonyl-CoA to flaviolin in yields up to 40% with a residence time of 6 min. This conversion is similar to that obtained in several-milliliter batch reactions after 2 h. Linking this microchannel to the SBP microchannel results in biflaviolin synthesis. During the course of this work, we discovered that the substrate specificity of THNS could be manipulated by simply changing the reaction pH. As a result, the starter acyl-CoA specificity can be broadened to yield a series of truncated pyrone products. When combined with variations in the ratio of acyl-CoA and malonyl-CoA (extender substrate) feed rates, high yields of the pyrone products could be achieved, which is further structurally diversified from self- and cross-coupling in the SBP microchannel. The ability to rapidly evaluate the effects of reaction conditions and synthetic multienzyme pathways on a microfludic platform provides a new paradigm for performing metabolic pathway engineering, namely, the reconstruction of pathways for use in new compound discovery.

Review of oxidative degradations of certain heterocyclic polymers

NASA Technical Reports Server (NTRS)

Mayo, F. R.

1971-01-01

The curing and decompositions of polyphenylenes and several nitrogen-containing condensation polymers, particularly polybenzimidazoles and pyrones, are reviewed critically. It is concluded that the condensations are usually imperfect and incomplete and that in most of the published work the late stages of the condensation are complicated by the beginnings of the charring and carbonization processes. Most discussions of mechanisms in this range are highly speculative and of little value. The most promising fields for further research are at lower temperatures, where slow oxidation processes deserve study, and at higher temperatures, where it may be possible to influence carbonization processes to obtain better products.

New isochaetochromin, an inhibitor of triacylglycerol synthesis in mammalian cells, produced by Penicillium sp. FKI-4942: I. Taxonomy, fermentation, isolation and biological properties.

PubMed

Ugaki, Narihiro; Matsuda, Daisuke; Yamazaki, Hiroyuki; Nonaka, Kenichi; Masuma, Rokuro; Omura, Satoshi; Tomoda, Hiroshi

2012-01-01

A new bis-naphtho-γ-pyrone isomer named isochaetochromin A(1) was isolated along with known isochaetochromins B(1) and B(2) from the culture broth of Penicillium sp. FKI-4942 by solvent extraction, silica gel column chromatography and HPLC. Among them, isochaetochromin B(1) showed the most potent inhibitory activity of triacylglycerol synthesis with an IC(50) value of 5.6 μM, followed by isochaetochromins B(2) (IC(50), 11 μM) and A(1) (33 μM).

Process for introducing electrical conductivity into high-temperature polymeric materials

DOEpatents

Liepins, R.; Jorgensen, B.S.; Liepins, L.Z.

1993-12-21

High-temperature electrically conducting polymers are described. The in situ reactions: AgNO[sub 3] + RCHO [yields] Ag + RCOOH and R[sub 3]M [yields] M + 3R, where M=Au or Pt have been found to introduce either substantial bulk or surface conductivity in high-temperature polymers. The reactions involving the R[sub 3]M were caused to proceed thermally suggesting the possibility of using laser means for initiating such reactions in selected areas or volumes of the polymeric materials. The polymers successfully investigated to date are polyphenylquinoxaline, polytolylquinoxaline, polyquinoline, polythiazole, and pyrone.

Two new constituents from Erigeron breviscapus.

PubMed

Li, Jing; Yu, De-Quan

2013-09-01

Two novel constituents, named erigeronones A (1) and B (2), together with apigenin-7-O-β-galacturonide (3), quercetin-7-O-β-glucuronide (4), quercetin-3-O-β-galacturonide (5), and eriodictyol-7-O-β-glucuronide (6), were isolated from the whole grass of Erigeron breviscapus (Vant) Hand.-Mazz (Compositae). Their structures were established on the basis of spectral analyses and comparison with the literature data. Both new compounds 1 and 2 possess a γ-pyrone moiety that is rare in nature. Compound 1 showed significant protective effect on H2O2-injured human umbilical vein endothelial cells.

New α-Pyridones with Quorum-Sensing Inhibitory Activity from Diversity-Enhanced Extracts of a Streptomyces sp. Derived from Marine Algae.

PubMed

Du, Yuqi; Sun, Jian; Gong, Qianhong; Wang, Yi; Fu, Peng; Zhu, Weiming

2018-02-28

Four new α-pyrones (1-4) and eight known analogues (5-12) were identified from the secondary metabolites of Streptomyces sp. OUCMDZ-3436 derived from the marine green algae Enteromorpha prolifera. Seven new α-pyridones (14-20) were constructed by diversity-oriented synthesis, which has been an effective approach to expanding the chemical space of natural-product-like compounds. Compounds 16, 17, 19, and 20 were found to have inhibitory effect on the gene expression controlled by quorum sensing in Pseudomonas aeruginosa QSIS-lasI.

Rasfonin, a novel 2-pyrone derivative, induces ras-mutated Panc-1 pancreatic tumor cell death in nude mice.

PubMed

Xiao, Z; Li, L; Li, Y; Zhou, W; Cheng, J; Liu, F; Zheng, P; Zhang, Y; Che, Y

2014-05-22

Rasfonin is a novel 2-pyrone derivative reported to induce apoptosis in ras-dependent cells. In this study, its effects on ras-mutated pancreatic cancer cells were investigated in vitro and in vivo. Two human pancreatic cancer cell lines Panc-1 (mutated K-ras) and BxPC-3 (wild-type K-ras) were selected to test the effects of rasfonin on cell proliferation, clone formation, migration and invasion in vitro. Immunoblotting was used to detect the expressions of EGFR-Ras-Raf-MEK-ERK signaling pathway proteins. Ras activity was measured using a pull-down ELISA kit and guanine exchange factor (GEF)/GTPase-activating proteins (GAP) activity was measured by [(3)H]-GDP radiometric ligand binding. For an in vivo study, CD1 nude mice bearing Panc-1 cells were treated with rasfonin or Salirasib (FTS). We found that rasfonin suppressed proliferation more strongly in Panc-1 cells (IC50=5.5 μM) than BxPC-3 cells (IC50=10 μM) in vitro. Clone formation, migration and invasion by Panc-1 cells were also reduced by rasfonin. Rasfonin had little effect on the farnesylation of Ras, but it strongly downregulated Ras activity and consequently phosphorylation of c-Raf/MEK/ERK. Further experiments indicated that rasfonin reduced Son of sevenless (Sos1) expression but did not alter GEF and GAP activities. The in vivo experiments also revealed that rasfonin (30 mg/kg) delayed the growth of xenograft tumors originating from Panc-1 cells. Tumor weight was ultimately decreased after 20 days of treatment of rasfonin. Rasfonin is a robust inhibitor of pancreatic cancers with the K-ras mutation. The reduction of Sos1 expression and the consequently depressed Ras-MAPK activity could be important in its anticancer activity.

Sinopestalotiollides A-D, cytotoxic diphenyl ether derivatives from plant endophytic fungus Pestalotiopsis palmarum.

PubMed

Xiao, Jian; Hu, Jia-Yao; Sun, Hao-Dong; Zhao, Xiang; Zhong, Wan-Tong; Duan, Dong-Zhu; Wang, Le; Wang, Xiao-Ling

2017-11-28

Four new diphenyl ether derivatives, sinopestalotiollides A-D (1-4), one new natural α-pyrone product (11), as well as twelve known compounds (5-1 7), were obtained from the ethyl acetate extract of the endophytic fungus Pestalotiopsis palmarum isolated from the leaves of medicinal plant Sinomenium acutum (Thunb.) Rehd et Wils. The structures were elucidated by HR-ESI-MS and NMR spectrometry data. Bioassay experiments revealed that compounds 1-4 and 11 exhibited strong to weak cytotoxicities against three human tumor cell lines Hela, HCT116 and A549. Copyright © 2017 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Solheim, B.A.

Three families of termites have the ability to produce a sticky secretion that envelopes and immobilizes the enemy. In the family Termitidae the secretion contains the diterpenoid hydrocarbons, kempene I and kempene II. The molecular structure of kempene II from the termite, Nasutitermes kempae, is described in detail. Another species of termite, Cubitermes umbratus, contained the diterpenoid hydrocarbon biflora-4,10-19,15-triene in the secretion and this compound is described. Studies were also conducted on the mucous secretion of the pedal gland of the marine nudibranch, Tidachiella diomedea. Tridachione, a substituted ..gamma..-pyrone, was isolated in the pure state and its molecular structure ismore » described in detail. (HLW)« less

[Research advances of Tasmayi].

PubMed

Kizaibek, Murat

2013-02-01

Tasmayi (mumie, shilajit) is a pale brown to black substance which leaks from the layers of rocks in many mountain ranges during the warm summer months. In traditional Kazakh medicine, it is used for the treatment of bone fracture and many inflammatory ailments. It is also used as a remedy in the traditional medical systems of many countries such as India, Russia and Kazakhstan. According to the literatures, Tasmayi possesses anti-inflammatory, antiulcerogenic, antibacterial, free radical scavenging, antioxidative, memory enhancing, antidiabetic, antistress, antiallergic, immunomodulative, anti AIDS, anabolic and regeneration stimulating activities. The major physiological action of Tasmayi could be belonging to the presence of dibenzo-alpha-pyrones along with humic and fulvic acids.

14-Meth­oxy-4,6-dimethyl-9-phenyl-8,12-dioxa-4,6-di­aza­tetra­cyclo­[8.8.0.02,7.013,18]octa­deca-2(7),13,15,17-tetra­ene-3,5,11-trione

PubMed Central

Jagadeesan, G; Jayashree, S.; Kannan, D.; Bakthadoss, M.; Aravindhan, S.

2013-01-01

The title compound, C23H20N2O6, crystallizes with two mol­ecules in the asymmetric unit in which the dihedral angles between the mean planes of the pyran and phenyl rings are 66.6 (1) and 61.9 (1) °. The fused pyrone and pyran rings each adopts a sofa conformation. In the crystal, C—H⋯O hydrogen bonds link the mol­ecules, forming a two-dimensional network parallel to [001]. PMID:24109298

14-Eth­oxy-4,6-dimethyl-9-phenyl-8,12-dioxa-4,6-diaza­tetra­cyclo­[8.8.0.02,7.013,18]octa­deca-2(7),13,15,17-tetra­ene-3,5,11-trione

PubMed Central

Jagadeesan, G.; Kannan, D.; Bakthadoss, M.; Aravindhan, S.

2013-01-01

In the title compound, C23H20N2O6, the fused pyrone and pyran rings each adopt a sofa conformation. The dihedral angle between the mean planes of the pyran and phenyl rings is 61.9 (1)°. In the crystal, mol­ecules are linked by two pairs of C—H⋯O hydrogen bonds, forming dimers. These dimers are linked via a third C—H⋯O hydrogen bond, forming a two-dimensional network parallel to (10-2). PMID:23476462

Rasfonin, a novel 2-pyrone derivative, induces ras-mutated Panc-1 pancreatic tumor cell death in nude mice

PubMed Central

Xiao, Z; Li, L; Li, Y; Zhou, W; Cheng, J; Liu, F; Zheng, P; Zhang, Y; Che, Y

2014-01-01

Rasfonin is a novel 2-pyrone derivative reported to induce apoptosis in ras-dependent cells. In this study, its effects on ras-mutated pancreatic cancer cells were investigated in vitro and in vivo. Two human pancreatic cancer cell lines Panc-1 (mutated K-ras) and BxPC-3 (wild-type K-ras) were selected to test the effects of rasfonin on cell proliferation, clone formation, migration and invasion in vitro. Immunoblotting was used to detect the expressions of EGFR–Ras–Raf–MEK–ERK signaling pathway proteins. Ras activity was measured using a pull-down ELISA kit and guanine exchange factor (GEF)/GTPase-activating proteins (GAP) activity was measured by [3H]-GDP radiometric ligand binding. For an in vivo study, CD1 nude mice bearing Panc-1 cells were treated with rasfonin or Salirasib (FTS). We found that rasfonin suppressed proliferation more strongly in Panc-1 cells (IC50=5.5 μM) than BxPC-3 cells (IC50=10 μM) in vitro. Clone formation, migration and invasion by Panc-1 cells were also reduced by rasfonin. Rasfonin had little effect on the farnesylation of Ras, but it strongly downregulated Ras activity and consequently phosphorylation of c-Raf/MEK/ERK. Further experiments indicated that rasfonin reduced Son of sevenless (Sos1) expression but did not alter GEF and GAP activities. The in vivo experiments also revealed that rasfonin (30 mg/kg) delayed the growth of xenograft tumors originating from Panc-1 cells. Tumor weight was ultimately decreased after 20 days of treatment of rasfonin. Rasfonin is a robust inhibitor of pancreatic cancers with the K-ras mutation. The reduction of Sos1 expression and the consequently depressed Ras–MAPK activity could be important in its anticancer activity. PMID:24853419

Deciphering the chemoselectivity of nickel-dependent quercetin 2,4-dioxygenase.

PubMed

Wang, Wen-Juan; Wei, Wen-Jie; Liao, Rong-Zhen

2018-06-13

The reaction mechanism and chemoselectivity of nickel-dependent quercetin 2,4-dioxygenase (2,4-QueD) have been investigated using the QM/MM approach. The protonation state of the Glu74 residue, a first-shell ligand of Ni, has been considered to be either neutral or deprotonated. QM/MM calculations predict that Glu74 must be deprotonated to rationalize the chemoselectivity and steer the 2,4-dioxygenolytic cleavage of quercetin, which harvests the experimentally-observed product, 2-protocatechuoylphloroglucinol carboxylic acid, coupled with the release of carbon monoxide. If the enzyme has a neutral Glu74 residue, the undesired 2,3-dioxygenolytic cleavage of quercetin becomes the dominant pathway, leading to the formation of α-keto acid. The calculations suggest that the reaction takes place via three major steps: (1) attack of the superoxide on the C2 of the substrate pyrone ring to generate a NiII-peroxide intermediate; (2) formation of the second C-O bond between C4 and the peroxide to produce a peroxide bridge; (3) simultaneous cleavage of the C2-C3, C3-C4, and O1-O2 bonds with the formation of 2-protocatechuoylphloroglucinol carboxylic acid and carbon monoxide. The third step was found to be rate-limiting, with a barrier of 17.4 kcal mol-1, which is in very good agreement with the experimental kinetic data. For the second C-O bond formation, an alternative pathway is that the peroxide attacks the C3 of the substrate pyrone ring, leading to the formation of a four-membered ring intermediate, which then undergoes concerted C2-C3 and O1-O2 bond cleavages to produce an α-keto acid. This pathway is associated with a barrier of 30.6 kcal mol-1, which is much higher than the major pathway. When Glu74 is protonated, the 2,3-dioxygenolytic pathway, however, has a lower barrier (21.8 kcal mol-1) than the 2,4-dioxygenolytic pathway.

Pericocins A-D, New Bioactive Compounds from Periconia sp.

PubMed

Wu, Yue-Hua; Xiao, Gao-Keng; Chen, Guo-Dong; Wang, Chuan-Xi; Hu, Dan; Lian, Yun-Yang; Lin, Feng; Guo, Liang-Dong; Yao, Xin-Sheng; Gao, Hao

2015-12-01

One new dihydroisocoumarin, pericocin A (1), one new chromone, pericocin B (2), and two new α-pyrone derivatives, pericocins C-D (3-4), together with two known compounds, 3-(2-oxo-2H-pyran-6-yl)propanoic acid (5) and (E)-3-(2-oxo-2H-pyran-6-yl)acrylic acid (6), were isolated from the culture of the endolichenic fungus Periconia sp.. Their structures were elucidated by spectroscopic methods. All these compounds are derived from the polyketone biosynthetic pathway. Compound 1 was obtained as a mixture of enantiomers. The antimicrobial activity of compounds 1-5 was tested against Escherichia coli, Staphylococcus aureus, Aspergillus niger, and Candida albicans. Compounds 1-5 showed moderate antimicrobial activity against A. niger and weak activity against C. albicans.

Mycotoxins from mould infested building materials.

PubMed

Nielsen, K F

2000-03-01

Only limited documentation of non-allergenic, especially toxic reactions after inhalation of microfungal spores in water damaged buildings exists. Recently attention has been drawn to the mycotoxins as causal compounds, as some the dominating genera found in buildings are well known mycotoxin producers.Penicillium chrysogenum and A. ustus do not seem to produce any known mycotoxins when growing on building materials, whereasP. brevicompactum produces mycophenolic acid, someP. polonicum produces verrucosidin and verrucofortine,A. versicolor produces sterigmatocystins,A. niger produces nigragillin, orlandin, naphtho-γ-pyrones and tetracyclic compounds, someA. ochraceus produces ochratoxin A,Alternaria spp. produce alternariol and alternariol monomethyl ether,Chaetomium globosum produce chaetoglobosins, and finally 30-40% ofStachybotrys chartarum isolates from buildings produce macrocyclic trichothecenes and a number of other biologically active compounds.

Antibiotic Extraction as a Recent Biocontrol Method for Aspergillus Niger andAspergillus Flavus Fungi in Ancient Egyptian mural paintings

NASA Astrophysics Data System (ADS)

Hemdan, R. Elmitwalli; Fatma, Helmi M.; Rizk, Mohammed A.; Hagrassy, Abeer F.

Biodeterioration of mural paintings by Aspergillus niger and Aspergillus flavus Fungi has been proved in different mural paintings in Egypt nowadays. Several researches have studied the effect of fungi on mural paintings, the mechanism of interaction and methods of control. But none of these researches gives us the solution without causing a side effect. In this paper, for the first time, a recent treatment by antibiotic "6 penthyl α pyrone phenol" was applied as a successful technique for elimination of Aspergillus niger and Aspergillus flavus. On the other hand, it is favorable for cleaning Surfaces of Murals executed by tembera technique from the fungi metabolism which caused a black pigments on surfaces.

2H-pyran-2-one and 2H-furan-2-one derivatives from the plant endophytic fungus Pestalotiopsis fici.

PubMed

Liu, Shuchun; Liu, Xiangyu; Guo, Liangdong; Che, Yongsheng; Liu, Ling

2013-11-01

Two new α-pyrones (=2H-pyran-2-ones), ficipyrones A and B (1 and 2, resp.), and two new α-furanones (=2H-furan-2-ones), ficifuranones A and B (3 and 4, resp.), together with three known metabolites, antibiotic F 0368 (5), hydroxyseiridin (6), and hydroxyisoseiridin (7), were isolated from solid cultures of the plant endophytic fungus Pestalotiopsis fici. Their structures were elucidated primarily by NMR spectroscopy, and the absolute configuration of 1 was deduced from the circular-dichroism (CD) data. Compound 1 showed antifungal activity against the plant pathogen Gibberella zeae (CGMCC 3.2873) with an IC50 value of 15.9 μM. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

Secondary Metabolites Produced by an Endophytic Fungus Pestalotiopsis sydowiana and Their 20S Proteasome Inhibitory Activities.

PubMed

Xia, Xuekui; Kim, Soonok; Liu, Changheng; Shim, Sang Hee

2016-07-20

Fungal endophytes have attracted attention due to their functional diversity. Secondary metabolites produced by Pestalotiopsis sydowiana from a halophyte, Phragmites communis Trinus, were investigated. Eleven compounds, including four penicillide derivatives (1-4) and seven α-pyrone analogues (5-10) were isolated from cultures of P. sydowiana. The compounds were identified based on spectroscopic data. The inhibitory activities against the 20S proteasome were evaluated. Compounds 1-3, 5, and 9-10 showed modest proteasome inhibition activities, while compound 8 showed strong activity with an IC50 of 1.2 ± 0.3 μM. This is the first study on the secondary metabolites produced by P. sydowiana and their proteasome inhibitory activities. The endophytic fungus P. sydowiana might be a good resource for proteasome inhibitors.

Coupling chemical and biological catalysis: a flexible paradigm for producing biobased chemicals.

PubMed

Schwartz, Thomas J; Shanks, Brent H; Dumesic, James A

2016-04-01

Advances in metabolic engineering have allowed for the development of new biological catalysts capable of selectively de-functionalizing biomass to yield platform molecules that can be upgraded to biobased chemicals using high efficiency continuous processing allowed by heterogeneous chemical catalysis. Coupling these disciplines overcomes the difficulties of selectively activating COH bonds by heterogeneous chemical catalysis and producing petroleum analogues by biological catalysis. We show that carboxylic acids, pyrones, and alcohols are highly flexible platforms that can be used to produce biobased chemicals by this approach. More generally, we suggest that molecules with three distinct functionalities may represent a practical upper limit on the extent of functionality present in the platform molecules that serve as the bridge between biological and chemical catalysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

The complete mitochondrial genome of Acanthosaura lepidogaster (Squamata: Agamidae).

PubMed

Yu, Xiu-Li; Du, Yu; Yao, Yun-Tao; Lin, Chi-Xian; Lin, Long-Hui

2017-03-01

In this paper, we report the complete mitochondrial genome of Acanthosaura lepidogaster (Squamata, Agamidae), which is a circular molecule of 16 899 bp in size and consists of 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and a control region. The overall base composition is as follows: T (22.8%), C (30.5%), A (32.3%), and G (14.4%). We constructed a phylogeny that included for 10 species of Leiolepidinae lizards and one outgroup Leiocephalus personatus constructed in BEAST, based on 15 mitochondrial genes (12S, 16S, ND1, ND2, COI, COII, ATP8, ATP6, COIII, ND3, ND4L, ND4, ND5, ND6, and cytochrome b). The topology of the phylogenetic tree is broadly similar to that mentioned by Pyron et al.

Fungi as a source of natural coumarins production.

PubMed

Costa, Tania Maria; Tavares, Lorena Benathar Ballod; de Oliveira, Débora

2016-08-01

Natural coumarins and derivatives are compounds that occur naturally in several organisms (plant, bacteria, and fungi) consisting of fused benzene and α-pyrone rings. These compounds show high technological potential applications in agrochemical, food, pharmaceuticals, and cosmetics industries. Therefore, the need for bulk production of coumarins and the advancement of the chemical and pharmaceutical industries led to the development of synthetic coumarin. However, biotransformation process, synthetic bioengineering, metabolic engineering, and bioinformatics have proven effective in the production of natural products. Today, these biological systems are recognized as green chemistry innovation and business strategy. This review article aims to report the potential of fungi for synthesis of coumarin. These microorganisms are described as a source of natural products capable of synthesizing many bioactive metabolites. The features, classification, properties, and industrial applications of natural coumarins as well as new molecules obtained by basidiomycetes and ascomycetes fungi are reported in order to explore a topic not yet discussed in the scientific literature.

Separation and purification of bioactive botrallin and TMC-264 by a combination of HSCCC and semi-preparative HPLC from endophytic fungus Hyalodendriella sp. Ponipodef12.

PubMed

Mao, Ziling; Luo, Ruiya; Luo, Haiyu; Tian, Jin; Liu, Hongwei; Yue, Yang; Wang, Mingan; Peng, Youliang; Zhou, Ligang

2014-09-01

Two dibenzo-α-pyrones, botrallin (1) and TMC-264 (2) were preparatively separated from crude ethyl acetate extract of the endophytic fungus Hyalodendriella sp. Ponipodef12, which was isolated from the hybrid 'Neva' of Populus deltoides Marsh × P. nigra L. using a combination of high-speed counter-current chromatography (HSCCC) and semi-preparative HPLC. Botrallin (1) with 74.73% of purity and TMC-264 (2) with 82.29% of purity were obtained through HSCCC by employing a solvent system containing n-hexane-ethyl acetate-methanol-water at a volume ratio of 1.2:1.0:0.9:1.0. It was the first time for TMC-264 (2) to be isolated from this fungus. TMC-264 (2) showed strong antimicrobial and antinematodal activity, and botrallin (1) exhibited moderate inhibitory activity on acetylcholinesterase.

Arzanol, a Potent mPGES-1 Inhibitor: Novel Anti-Inflammatory Agent

PubMed Central

Kothavade, Pankaj S.; Nagmoti, Dnyaneshwar M.; Bulani, Vipin D.; Juvekar, Archana R.

2013-01-01

Arzanol is a novel phloroglucinol α-pyrone, isolated from a Mediterranean plant Helichrysum italicum (Roth) Don ssp. microphyllum which belongs to the family Asteraceae. Arzanol has been reported to possess a variety of pharmacological activities. However, anti-inflammatory, anti-HIV, and antioxidant activities have been studied in some detail. Arzanol has been reported to inhibit inflammatory transcription factor NFκB activation, HIV replication in T cells, releases of IL-1β, IL-6, IL-8, and TNF-α, and biosynthesis of PGE2 by potentially inhibiting mPGES-1 enzyme. Diversity of mechanisms of actions of arzanol may be useful in treatment of disease involving these inflammatory mediators such as autoimmune diseases and cancer. This review presents comprehensive information on the chemistry, structure-activity relationship, and pharmacological activities of arzanol. In addition this review discusses recent developments and the scope for future research in these aspects. PMID:24198734

Development of easy made low cost bindless monolithic electrodes from biomass with controlled properties to be used as electrochemical capacitors.

PubMed

Nabais, J M Valente; Teixeira, Jorge Ginja; Almeida, I

2011-02-01

The aim of the work now reported is the development of low cost electrodes in the monolithic shape without the need for a pos-production step with potential to be used in supercapacitors. The tested materials were activated carbon fibres prepared and activated carbons made from coffee endocarp. The main functional groups identified were quinone, lactone, Si-H, phenol, hydroxyl, carbonyl and ether for activated carbon samples and amine, amide, pyrone, lactone, carbonyl and hydroxyl for activated carbon fibres samples. The nanostructure of the materials is predominantly microporous but with a significant variety of porosity development with BET surface area and pore volume given by α(s) method range from 89 to 1050 m(2) g(-1) and 0.04 to 0.50 cm(3) g(-1), respectively. The electrochemical properties of the materials were investigated using classic cyclic voltammetry, chronopotentiometry and electrochemical impedance spectroscopy. The higher specific capacitance achieved was 176 F g(-1). Copyright © 2010 Elsevier Ltd. All rights reserved.

Safety and efficacy of shilajit (mumie, moomiyo).

PubMed

Stohs, Sidney J

2014-04-01

Shilajit (mumie; moomiyo, mummiyo) has been used for a wide variety of illnesses and conditions for many years. However, relatively few well-controlled human studies have been conducted on the effects of shiliajit, although a growing number of studies have been published in recent years involving animal and in vitro systems. The safety of shilajit is well documented based on animal and human studies. Various research studies indicate that shilajit exhibits antioxidant, anti-inflammatory, adaptogenic, immunomodulatory, and anti-dyslipidemic properties. Animal and human studies indicate that shilajit enhances spermatogenesis. Furthermore, animal and human data support its use as a 'revitalizer', enhancing physical performance and relieving fatigue with enhanced production of ATP. Key constituents in shilajit responsible for these effects appear to be dibenzo-α-pyrones and fulvic acid and their derivatives. Various mechanistic studies provide support for the above observed effects. Additional well-controlled human and animal studies involving the use of standardized products are needed. Copyright © 2013 John Wiley & Sons, Ltd.

[Degradation of antipyrin by pyrazon-degrading bacteria (author's transl)].

PubMed

Sauber, K; Müller, R; Keller, E; Eberspächer, J; Lingens, F

1977-01-01

Bacteria with the ability to grow on pyrazon as sole source of carbon were isolated from soil. They also are able to grow on antipyrin. Then three metabolites of antipyrin can be isolated from the culture fluid which were identified as 2,3-dimethyl-1-(cis-2,3-dihydro-2,3-dihydroxy-4,6-cyclohexadiene-1-yl)-pyrazolone (5) (I), as 2,3-dimethyl-1-(2,3-dihydroxyphenyl)-pyrazolone (5) (II) and as 2,3-dimethyl-pyrazolone (5) (III), respectively. Compound I and II were used as substrates for enzyme studies. A dioxygenase catalyzes the enzymatic conversion of antipyrin into compound I. In the presence of NAD as cosubstrate compound I is transformed into compound II by a dehydrogenase. A pure preparation of metapyrocatechase from pyrazon-degrading bacteria converts compound II into the dephenylated heterocyclic moiety of antipyrin (III) and into 2-pyrone-6-carboxylic acid. Based on the results of the enzymatic studies a pathway for the degradation of antipyrin is proposed.

New Butyrolactone Type Lignans from Arctii Fructus and Their Anti-inflammatory Activities.

PubMed

Yang, Ya-Nan; Huang, Xiao-Ying; Feng, Zi-Ming; Jiang, Jian-Shuang; Zhang, Pei-Cheng

2015-09-16

Arctiidilactone (1), a novel rare butyrolactone lignan with a 6-carboxyl-2-pyrone moiety, and 11 new butyrolactone lignans (2-12) were isolated from the fruits of Arctium lappa L., together with 5 known compounds (13-17). Their structures were elucidated by interpretation of their spectroscopic data (1D and 2D NMR, UV, IR, ORD, and HRESIMS) and comparison to literature data. The absolute configurations of compounds 1-12 were determined by a combination of rotating-frame nuclear Overhauser effect spectroscopy (ROESY), circular dichroism (CD) spectroscopy, and Rh2(OCOCF3)4-induced CD spectroscopy. All of the compounds were tested for their anti-inflammatory properties in terms of suppressing the production of NO in lipopolysaccharide-induced BV2 cells. Compounds 1, 6, 8, and 10 exhibited stronger anti-inflammatory effects than the positive control curcumin, particularly 1, which exhibited 75.51, 70.72, and 61.17% inhibition at 10, 1, and 0.1 μM, respectively.

4′,5-Dihy­droxy-7-meth­oxy­flavanone dihydrate

PubMed Central

Brito, Iván; Bórquez, Jorge; Simirgiotis, Mario; Cárdenas, Alejandro; López-Rodríguez, Matías

2012-01-01

The title compound, C16H14O5·2H2O [systematic name: 5-hy­droxy-2-(4-hy­droxy­phen­yl)-7-meth­oxy­chroman-4-one dihydrate], is a natural phytoalexin flavone isolated from the native chilean species Heliotropium taltalense and crystallizes with an organic mol­ecule and two water mol­ecules in the asymmetric unit. The 5-hy­droxy group forms a strong intra­molecular hydrogen bond with the carbonyl group, resulting in a six-membered ring. In the crystal, the components are linked by O—H⋯O hydrogen bonds, forming a three-dimensional network. The 4-hy­droxy­phenyl benzene ring is bonded equatorially to the pyrone ring, which adopts a slightly distorted sofa conformation. The title compound is the hydrated form of a previously reported structure [Shoja (1990 ▶). Acta Cryst. C46, 1969–1971]. There are only slight variations in the mol­ecular geometry between the two compounds. PMID:22259537

Heterologous expression of the avirulence gene ACE1 from the fungal rice pathogen Magnaporthe oryzae † †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4sc03707c Click here for additional data file.

PubMed Central

Song, Zhongshu; Bakeer, Walid; Marshall, James W.; Yakasai, Ahmed A.; Khalid, Rozida Mohd; Collemare, Jerome; Skellam, Elizabeth; Tharreau, Didier; Lebrun, Marc-Henri; Lazarus, Colin M.; Bailey, Andrew M.; Simpson, Thomas J.

2015-01-01

The ACE1 and RAP1 genes from the avirulence signalling gene cluster of the rice blast fungus Magnaporthe oryzae were expressed in Aspergillus oryzae and M. oryzae itself. Expression of ACE1 alone produced a polyenyl pyrone (magnaporthepyrone), which is regioselectively epoxidised and hydrolysed to give different diols, 6 and 7, in the two host organisms. Analysis of the three introns present in ACE1 determined that A. oryzae does not process intron 2 correctly, while M. oryzae processes all introns correctly in both appressoria and mycelia. Co-expression of ACE1 and RAP1 in A. oryzae produced an amide 8 which is similar to the PKS-NRPS derived backbone of the cytochalasans. Biological testing on rice leaves showed that neither the diols 6 and 7, nor amide 8 was responsible for the observed ACE1 mediated avirulence, however, gene cluster analysis suggests that the true avirulence signalling compound may be a tyrosine-derived cytochalasan compound. PMID:29142718

Application of off-line two-dimensional high-performance countercurrent chromatography on the chloroform-soluble extract of Cuscuta auralis seeds.

PubMed

Rho, Taewoong; Yoon, Kee Dong

2018-05-01

In this study, the chloroform-soluble extract of Cuscuta auralis was separated successfully using off-line two-dimensional high-performance countercurrent chromatography, yielding a γ-pyrone, two alkaloids, a flavonoid, and four lignans. The first-dimensional countercurrent separation using a methylene chloride/methanol/water (11:6:5, v/v/v) system yielded three subfractions (fractions I-III). The second-dimensional countercurrent separations, conducted on fractions I-III using n-hexane/ethyl acetate/methanol/water/acetic acid (5:5:5:5:0, 3:7:3:7:0, and 1:9:1:9:0.01, v/v/v/v/v) systems, gave maltol (1), (-)-(13S)-cuscutamine (2), (+)-(13R)-cuscutamine (3), (+)-pinoresinol (4), (+)-epipinoresinol (5), kaempferol (6), piperitol (7), and (9R)-hydroxy-d-sesamin (8). To the best of our knowledge, maltol was identified for the first time in Cuscuta species. Furthermore, this report details the first full assignment of spectroscopic data of two cuscutamine epimers, (-)-(13S)-cuscutamine and (+)-(13R)-cuscutamine. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Empirical valence bond models for reactive potential energy surfaces: a parallel multilevel genetic program approach.

PubMed

Bellucci, Michael A; Coker, David F

2011-07-28

We describe a new method for constructing empirical valence bond potential energy surfaces using a parallel multilevel genetic program (PMLGP). Genetic programs can be used to perform an efficient search through function space and parameter space to find the best functions and sets of parameters that fit energies obtained by ab initio electronic structure calculations. Building on the traditional genetic program approach, the PMLGP utilizes a hierarchy of genetic programming on two different levels. The lower level genetic programs are used to optimize coevolving populations in parallel while the higher level genetic program (HLGP) is used to optimize the genetic operator probabilities of the lower level genetic programs. The HLGP allows the algorithm to dynamically learn the mutation or combination of mutations that most effectively increase the fitness of the populations, causing a significant increase in the algorithm's accuracy and efficiency. The algorithm's accuracy and efficiency is tested against a standard parallel genetic program with a variety of one-dimensional test cases. Subsequently, the PMLGP is utilized to obtain an accurate empirical valence bond model for proton transfer in 3-hydroxy-gamma-pyrone in gas phase and protic solvent. © 2011 American Institute of Physics

Ecological functions of Trichoderma spp. and their secondary metabolites in the rhizosphere: interactions with plants.

PubMed

Contreras-Cornejo, Hexon Angel; Macías-Rodríguez, Lourdes; del-Val, Ek; Larsen, John

2016-04-01

Trichodermaspp. are common soil and root inhabitants that have been widely studied due to their capacity to produce antibiotics, parasitize other fungi and compete with deleterious plant microorganisms. These fungi produce a number of secondary metabolites such as non-ribosomal peptides, terpenoids, pyrones and indolic-derived compounds. In the rhizosphere, the exchange and recognition of signaling molecules byTrichodermaand plants may alter physiological and biochemical aspects in both. For example, severalTrichodermastrains induce root branching and increase shoot biomass as a consequence of cell division, expansion and differentiation by the presence of fungal auxin-like compounds. Furthermore,Trichoderma, in association with plant roots, can trigger systemic resistance and improve plant nutrient uptake. The present review describes the most recent advances in understanding the ecological functions ofTrichodermaspp. in the rhizosphere at biochemical and molecular levels with special emphasis on their associations with plants. Finally, through a synthesis of the current body of work, we present potential future research directions on studies related toTrichodermaspp. and their secondary metabolites in agroecosystems. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Determination of starting materials, intermediates, and subsidiary colors in the color additive Food Red No. 106 (Sulforhodamine B) using high-performance liquid chromatography.

PubMed

Tatebe, Chiye; Ohtsuki, Takashi; Fujita, Tsuyoshi; Nishiyama, Koji; Itoh, Sumio; Sugimoto, Naoki; Kubota, Hiroki; Tada, Atsuko; Sato, Kyoko; Akiyama, Hiroshi

2017-12-15

The main subsidiary color of structure in Food Red No. 106 (R106) was identified to be a desethyl derivative (R106-SubA). High-performance liquid chromatography (HPLC) was performed for the quantitative determination of benzaldehyde-2,4-disulfonic acid, N,N-diethyl-m-aminophenol, leuco acid, pyrone acid, R106-SubA, etc. in R106. An ammonium acetate solution (20mM) and acetonitrile:water (7:3) were used to stabilize the retention time of the HPLC analytes. The linearity of the calibration curves was in the range of 0.05-10μg/mL, with good correlation coefficients (R 2 >0.9983). The recoveries of impurities at levels 0.1%, 0.5% and 1% ranged from 94.2% to 106.6% with relative standard deviations of 0.1%-1.0%. While surveying commercial R106, the amounts obtained by area% determination were similar to those obtained by the calibration-curve determination. The area% determination by HPLC for the determinations of impurities in R106 is a simple and reliable method and can be applied in routine analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bioprospecting of Novel and Bioactive Compounds from Marine Actinomycetes Isolated from South China Sea Sediments.

PubMed

Yang, Na; Song, Fuhang

2018-02-01

Marine actinomycetes are less investigated compared to terrestrial strains as potential sources of natural products. To date, few investigations have been performed on culturable actinomycetes associated with South China Sea sediments. In the present study, twenty-eight actinomycetes were recovered from South China Sea sediments after dereplication by traditional culture-dependent method. The 16S rRNA gene sequences analyses revealed that these strains related to five families and seven genera. Twelve representative strains possessed at least one of the biosynthetic genes coding for polyketide synthase I, II, and nonribosomal peptide synthetase. Four strains had anti-Mycobacterium phlei activities and five strains had activities against methicillin-resistant Staphylococcus aureus. 10 L-scale fermentation of strains Salinispora sp. NHF45, Nocardiopsis sp. NHF48, and Streptomyces sp. NHF86 were carried out for novel and bioactive compounds discovery. Finally, we obtained a novel α-pyrone compound from marine Nocardiopsis sp. NHF48, an analogue of paulomenol from marine Streptomyces sp. NHF86 and a new source of rifamycin B, produced by Salinispora sp. NHF45. The present study concluded that marine actinomycetes, which we isolated from South China Sea sediments, will be a suitable source for the development of novel and bioactive compounds.

Metabolites of Trichoderma species isolated from damp building materials.

PubMed

McMullin, David R; Renaud, Justin B; Barasubiye, Tharcisse; Sumarah, Mark W; Miller, J David

2017-07-01

Buildings that have been flooded often have high concentrations of Trichoderma spores in the air while drying. Inhaled spores and spore and mycelial fragments contain large amounts of fungal glucan and natural products that contribute to the symptoms associated with indoor mould exposures. In this study, we considered both small molecules and peptaibol profiles of T. atroviride, T. koningiopsis, T. citrinoviride, and T. harzianum strains obtained from damp buildings in eastern Canada. Twenty-residue peptaibols and sorbicillin-derived metabolites (1-6) including a new structure, (R)-vertinolide (1), were characterized from T. citrinoviride. Trichoderma koningiopsis produced several koninginins (7-10), trikoningin KA V, and the 11-residue lipopeptaibols trikoningin KB I and trikoningin KB II. Trichoderma atroviride biosynthesized a mixture of 19-residue trichorzianine-like peptaibols, whereas T. harzianum produced 18-residue trichokindin-like peptaibols and the 11-residue harzianin HB I that was subsequently identified from the studied T. citrinoviride strain. Two α-pyrones, 6-pentyl-pyran-2-one (11) and an oxidized analog (12), were produced by both T. atroviride and T. harzianum. Aside from exposure to low molecular weight natural products, inhalation of Trichoderma spores and mycelial fragments may result in exposure to membrane-disrupting peptaibols. This investigation contributes to a more comprehensive understanding of the biologically active natural products produced by fungi commonly found in damp buildings.

Trichoderma volatiles effecting Arabidopsis: from inhibition to protection against phytopathogenic fungi

PubMed Central

Kottb, Metwally; Gigolashvili, Tamara; Großkinsky, Dominik K.; Piechulla, Birgit

2015-01-01

Trichoderma species are present in many ecosystems and some strains have the ability to reduce the severity of plant diseases by activating various defense pathways via specific biologically active signaling molecules. Hence we investigated the effects of low molecular weight volatile compounds of Trichoderma asperellum IsmT5 on Arabidopsis thaliana. During co-cultivation of T. asperellum IsmT5 without physical contact to A. thaliana we observed smaller but vital and robust plants. The exposed plants exhibit increased trichome numbers, accumulation of defense-related compounds such as H2O2, anthocyanin, camalexin, and increased expression of defense-related genes. We conclude that A. thaliana perceives the Trichoderma volatiles as stress compounds and subsequently initiates multilayered adaptations including activation of signaling cascades to withstand this environmental influence. The prominent headspace volatile of T. asperellum IsmT5 was identified to be 6-pentyl-α-pyrone (6PP), which was solely applied to A. thaliana to verify the growth and defense reactions. Most noticeable is that A. thaliana preexposed to 6PP showed significantly reduced symptoms when challenged with Botrytis cinerea and Alternaria brassicicola, indicating that defense-activated plants subsequently became more resistant to pathogen attack. Together, these results support that products that are based on Trichoderma volatiles have the potential being a useful biocontrol agent in agriculture. PMID:26483761

Signaling via the Trichoderma atroviride mitogen-activated protein kinase Tmk 1 differentially affects mycoparasitism and plant protection.

PubMed

Reithner, Barbara; Schuhmacher, Rainer; Stoppacher, Norbert; Pucher, Marion; Brunner, Kurt; Zeilinger, Susanne

2007-11-01

Trichoderma atroviride is a mycoparasite of a number of plant pathogenic fungi thereby employing morphological changes and secretion of cell wall degrading enzymes and antibiotics. The function of the tmk 1 gene encoding a mitogen-activated protein kinase (MAPK) during fungal growth, mycoparasitic interaction, and biocontrol was examined in T. atroviride. Deltatmk 1 mutants exhibited altered radial growth and conidiation, and displayed de-regulated infection structure formation in the absence of a host-derived signal. In confrontation assays, tmk 1 deletion caused reduced mycoparasitic activity although attachment to Rhizoctonia solani and Botrytis cinerea hyphae was comparable to the parental strain. Under chitinase-inducing conditions, nag 1 and ech 42 transcript levels and extracellular chitinase activities were elevated in a Deltatmk 1 mutant, whereas upon direct confrontation with R. solani or B. cinerea a host-specific regulation of ech 42 transcription was found and nag 1 gene transcription was no more inducible over an elevated basal level. Deltatmk 1 mutants exhibited higher antifungal activity caused by low molecular weight substances, which was reflected by an over-production of 6-pentyl-alpha-pyrone and peptaibol antibiotics. In biocontrol assays, a Deltatmk 1 mutant displayed a higher ability to protect bean plants against R. solani.

New natural products identified by combined genomics-metabolomics profiling of marine Streptomyces sp. MP131-18.

PubMed

Paulus, Constanze; Rebets, Yuriy; Tokovenko, Bogdan; Nadmid, Suvd; Terekhova, Larisa P; Myronovskyi, Maksym; Zotchev, Sergey B; Rückert, Christian; Braig, Simone; Zahler, Stefan; Kalinowski, Jörn; Luzhetskyy, Andriy

2017-02-10

Marine actinobacteria are drawing more and more attention as a promising source of new natural products. Here we report isolation, genome sequencing and metabolic profiling of new strain Streptomyces sp. MP131-18 isolated from marine sediment sample collected in the Trondheim Fjord, Norway. The 16S rRNA and multilocus phylogenetic analysis showed that MP131-18 belongs to the genus Streptomyces. The genome of MP131-18 isolate was sequenced, and 36 gene clusters involved in the biosynthesis of 18 different types of secondary metabolites were predicted using antiSMASH analysis. The combined genomics-metabolics profiling of the strain led to the identification of several new biologically active compounds. As a result, the family of bisindole pyrroles spiroindimicins was extended with two new members, spiroindimicins E and F. Furthermore, prediction of the biosynthetic pathway for unusual α-pyrone lagunapyrone isolated from MP131-18 resulted in foresight and identification of two new compounds of this family - lagunapyrones D and E. The diversity of identified and predicted compounds from Streptomyces sp. MP131-18 demonstrates that marine-derived actinomycetes are not only a promising source of new natural products, but also represent a valuable pool of genes for combinatorial biosynthesis of secondary metabolites.

New natural products identified by combined genomics-metabolomics profiling of marine Streptomyces sp. MP131-18

PubMed Central

Paulus, Constanze; Rebets, Yuriy; Tokovenko, Bogdan; Nadmid, Suvd; Terekhova, Larisa P.; Myronovskyi, Maksym; Zotchev, Sergey B.; Rückert, Christian; Braig, Simone; Zahler, Stefan; Kalinowski, Jörn; Luzhetskyy, Andriy

2017-01-01

Marine actinobacteria are drawing more and more attention as a promising source of new natural products. Here we report isolation, genome sequencing and metabolic profiling of new strain Streptomyces sp. MP131-18 isolated from marine sediment sample collected in the Trondheim Fjord, Norway. The 16S rRNA and multilocus phylogenetic analysis showed that MP131-18 belongs to the genus Streptomyces. The genome of MP131-18 isolate was sequenced, and 36 gene clusters involved in the biosynthesis of 18 different types of secondary metabolites were predicted using antiSMASH analysis. The combined genomics-metabolics profiling of the strain led to the identification of several new biologically active compounds. As a result, the family of bisindole pyrroles spiroindimicins was extended with two new members, spiroindimicins E and F. Furthermore, prediction of the biosynthetic pathway for unusual α-pyrone lagunapyrone isolated from MP131-18 resulted in foresight and identification of two new compounds of this family – lagunapyrones D and E. The diversity of identified and predicted compounds from Streptomyces sp. MP131-18 demonstrates that marine-derived actinomycetes are not only a promising source of new natural products, but also represent a valuable pool of genes for combinatorial biosynthesis of secondary metabolites. PMID:28186197

[Adsorption mechanism of furfural onto modified rice husk charcoals].

PubMed

Deng, Yong; Wang, Xianhua; Li, Yunchao; Shao, Jing'ai; Yang, Haiping; Chen, Hanping

2015-10-01

To evaluate the absorptive characteristics of furfural onto biomass charcoals derived from rice husk pyrolysis, we studied the information of the structure and surface chemistry properties of the rice husk charcoals modified by thermal treatment under nitrogen and carbon dioxide flow and adsorption mechanism of furfural. The modified samples are labeled as RH-N2 and RH-CO2. Fresh rice husk charcoal sample (RH-450) and modified samples were characterized by elemental analysis, nitrogen adsorption-desorption isotherms, Fourier-transform infrared spectroscopy and Boehm titration. The results show that fresh rice husk charcoal obtained at 450 degrees C had a large number of organic groups on its surface and poor pore structure. After the modification under nitrogen and carbon dioxide flow, oxygenic organics in rice husk charcoals decompose further, leading to the reduction of acidic functional groups on charcoals surface, and the increase of the pyrone structures of the basic groups. Meanwhile, pore structure was improved significantly and the surface area was increased, especially for the micropores. This resulted in the increase of π-π dispersion between the surfaces of rice husk charcoals and furfural molecular. With making comprehensive consideration of π-π dispersion and pore structure, the best removal efficiency of furfural was obtained by rice husk charcoal modified under carbon dioxide flow.

A comparative study of aroma-active compounds between dark and milk chocolate: relationship to sensory perception.

PubMed

Liu, Jianbin; Liu, Mengya; He, Congcong; Song, Huanlu; Guo, Jia; Wang, Ye; Yang, Haiying; Su, Xiaoxia

2015-04-01

The most important aroma-active compounds of two types of chocolate and cocoa liquor used for their production were analysed by gas chromatography-olfactometry-mass spectrometry (GC-O-MS) and aroma extract dilution analysis (AEDA). Furthermore, the relationship between odorants and sensory perception of chocolate was measured by quantitative analysis, sensory evaluation and correlation analysis. In addition, some chemicals were added to the original dark or milk chocolate to validate their roles in the aroma property of chocolate. A total of 32 major aroma-active compounds were identified in the chocolate with the flavour dilution factors of 27-729 by AEDA, including seven aldehydes, six pyrazines, three pyrroles, four carboxylic acids, four lactones, two alcohols, two ketones, one ester, one pyrone, one furan and one sulfur-containing compound. Further quantitative analysis showed that dark chocolate had higher contents of pyrazine, pyrrole, carboxylic acids, alcohols and Strecker aldehydes, whereas the concentration of lactones, esters, long chain aldehydes and ketones were higher in the milk type. Differences in volatile composition and descriptive flavour attributes between the dark and milk chocolate were observed. The relationship between aroma-active compounds and sensory perception in the chocolate was verified. © 2014 Society of Chemical Industry.

Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by subunit shuffling of fungal polyketide synthases.

PubMed

Xu, Yuquan; Zhou, Tong; Zhang, Shuwei; Espinosa-Artiles, Patricia; Wang, Luoyi; Zhang, Wei; Lin, Min; Gunatilaka, A A Leslie; Zhan, Jixun; Molnár, István

2014-08-26

Combinatorial biosynthesis aspires to exploit the promiscuity of microbial anabolic pathways to engineer the synthesis of new chemical entities. Fungal benzenediol lactone (BDL) polyketides are important pharmacophores with wide-ranging bioactivities, including heat shock response and immune system modulatory effects. Their biosynthesis on a pair of sequentially acting iterative polyketide synthases (iPKSs) offers a test case for the modularization of secondary metabolic pathways into "build-couple-pair" combinatorial synthetic schemes. Expression of random pairs of iPKS subunits from four BDL model systems in a yeast heterologous host created a diverse library of BDL congeners, including a polyketide with an unnatural skeleton and heat shock response-inducing activity. Pairwise heterocombinations of the iPKS subunits also helped to illuminate the innate, idiosyncratic programming of these enzymes. Even in combinatorial contexts, these biosynthetic programs remained largely unchanged, so that the iPKSs built their cognate biosynthons, coupled these building blocks into chimeric polyketide intermediates, and catalyzed intramolecular pairing to release macrocycles or α-pyrones. However, some heterocombinations also provoked stuttering, i.e., the relaxation of iPKSs chain length control to assemble larger homologous products. The success of such a plug and play approach to biosynthesize novel chemical diversity bodes well for bioprospecting unnatural polyketides for drug discovery.

Characterization of acid functional groups of carbon dots by nonlinear regression data fitting of potentiometric titration curves

NASA Astrophysics Data System (ADS)

Alves, Larissa A.; de Castro, Arthur H.; de Mendonça, Fernanda G.; de Mesquita, João P.

2016-05-01

The oxygenated functional groups present on the surface of carbon dots with an average size of 2.7 ± 0.5 nm were characterized by a variety of techniques. In particular, we discussed the fit data of potentiometric titration curves using a nonlinear regression method based on the Levenberg-Marquardt algorithm. The results obtained by statistical treatment of the titration curve data showed that the best fit was obtained considering the presence of five Brønsted-Lowry acids on the surface of the carbon dots with constant ionization characteristics of carboxylic acids, cyclic ester, phenolic and pyrone-like groups. The total number of oxygenated acid groups obtained was 5 mmol g-1, with approximately 65% (∼2.9 mmol g-1) originating from groups with pKa < 6. The methodology showed good reproducibility and stability with standard deviations below 5%. The nature of the groups was independent of small variations in experimental conditions, i.e. the mass of carbon dots titrated and initial concentration of HCl solution. Finally, we believe that the methodology used here, together with other characterization techniques, is a simple, fast and powerful tool to characterize the complex acid-base properties of these so interesting and intriguing nanoparticles.

Chemical profile, radical scavenging and cytotoxic activity of yellow gentian leaves (Genitaneae luteaefolium) grown in northern regions of Montenegro.

PubMed

Balijagić, Jasmina; Janković, Teodora; Zdunić, Gordana; Bosković, Jelena; Savikin, Katarina; Godevac, Dejan; Stanojković, Tatjana; Jovancević, Miodrag; Menković, Nebojsa

2012-11-01

LC-ESI-MS and HPLC were used for the identification of the constituents from G. lutea leaves collected at different localities, as well as for quantification of the main compounds. Seven secoiridoids, five C-glucoflavones and three xanthones, were identified. Swertiamarin derivatives, namely eustomorusside (2), eustomoside (3) and septemfidoside (5), were detected in G. lutea for the first time. Concentrations of five constituents (swertiamarin, gentiopicrin, isovitexin, mangiferin and isogentisin) were determined. The relationship between concentrations of y-pyrones and altitude was observed with statistically significant correlation (r = 0.94). The extracts were also evaluated for their content of total phenolics, and antiradical and cytotoxic activities. The total phenolics content ranged from 7.7 to 12.7 mg GAE/g, and the IC50 values for DPPH radical scavenging activity varied between 0.45 to 2.02 mg/mL. The leaf extract exhibited moderate cytotoxic effects toward HeLa cells with an IC50 value of 41.1 microg/mL, while gentiopicrin, mangiferin and isogentisin exerted strong activity against HeLa cells, with IC50 values ranging from 5.7 to 8.8 microg/mL. The results confirm the traditional usage of G. lutea leaves and also suggest their possible utilization as hepatoprotective, hypoglycemic and anti-inflammatory agents.

γ-Pyrone compounds: flavonoids and maltol glucoside derivatives from Herniaria glabra L. collected in the Ternopil region of the Ukraine.

PubMed

Kozachok, Solomiia; Pecio, Łukasz; Kolodziejczyk-Czepas, Joanna; Marchyshyn, Svitlana; Nowak, Pawel; Mołdoch, Jarosław; Oleszek, Wiesław

2018-08-01

The phytochemical investigation of the whole plant extracts of Herniaria glabra L. (Caryophyllaceae) led to the identification and isolation of four known flavonoids, one known and three undescribed maltol derivatives, and benzyl β-gentiobioside. The structures were established by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. For the first time in Herniaria genus, as well as in Caryophylaceae family the presence of apiorutin {quercetin 3-O-[(D-apio-β-d-furanosyl-(1 → 2)-O-[-α-l-rhamnopyranosyl-(1 → 6)]-β-d-glucopyranoside]} and licoagroside B {maltol 3-O-[6-O-(3-hydroxy-3-methylglutaroyl)]-β-d-glucopyranoside} were revealed. Additionally, antioxidant actions of apiorutin, rutin, narcissin (isorhamentin 3-O-β-d-rutinoside) and licoagroside B were assessed in human blood plasma, exposed to the peroxynitrite-induced oxidative stress in vitro. The isolates partly reduced oxidative (oxidation of thiol groups) and nitrative (tyrosine nitration) damage to blood plasma proteins, decreased plasma lipid peroxidation as well as enhanced the non-enzymatic antioxidant capacity of blood plasma. No cytotoxicity of the examined substances towards peripheral blood mononuclear cells was found. Copyright © 2018 Elsevier Ltd. All rights reserved.

Signaling via the Trichoderma atroviride mitogen-activated protein kinase Tmk1 differentially affects mycoparasitism and plant protection

PubMed Central

Reithner, Barbara; Schuhmacher, Rainer; Stoppacher, Norbert; Pucher, Marion; Brunner, Kurt; Zeilinger, Susanne

2015-01-01

Trichoderma atroviride is a mycoparasite of a number of plant pathogenic fungi thereby employing morphological changes and secretion of cell wall degrading enzymes and antibiotics. The function of the tmk1 gene encoding a mitogen-activated protein kinase (MAPK) during fungal growth, mycoparasitic interaction, and biocontrol was examined in T. atroviride. Δtmk1 mutants exhibited altered radial growth and conidiation, and displayed de-regulated infection structure formation in the absence of a host-derived signal. In confrontation assays, tmk1 deletion caused reduced mycoparasitic activity although attachment to Rhizoctonia solani and Botrytis cinerea hyphae was comparable to the parental strain. Under chitinase-inducing conditions, nag1 and ech42 transcript levels and extracellular chitinase activities were elevated in a Δtmk1 mutant, whereas upon direct confrontation with R. solani or B. cinerea a host-specific regulation of ech42 transcription was found and nag1 gene transcription was no more inducible over an elevated basal level. Δtmk1 mutants exhibited higher antifungal activity caused by low molecular weight substances, which was reflected by an over-production of 6-pentyl-α-pyrone and peptaibol antibiotics. In biocontrol assays, a Δtmk1 mutant displayed a higher ability to protect bean plants against R. solani. PMID:17509915

Solid-state fermentation of agro-industrial wastes to produce bioorganic fertilizer for the biocontrol of Fusarium wilt of cucumber in continuously cropped soil.

PubMed

Chen, Lihua; Yang, Xingming; Raza, Waseem; Luo, Jia; Zhang, Fengge; Shen, Qirong

2011-02-01

Agro-industrial wastes of cattle dung, vinegar-production residue and rice straw were solid-state fermented by inoculation with Trichoderma harzianum SQR-T037 (SQR-T037) for production of bioorganic fertilizers containing SQR-T037 and 6-pentyl-α-pyrone (6PAP) to control Fusarium wilt of cucumber in a continuously cropped soil. Fermentation days, temperature, inoculum and vinegar-production residue demonstrated significant effects on the SQR-T037 biomass and the yield of 6PAP, based on fractional factorial design. Three optimum conditions for producing the maximum SQR-T037 biomass and 6PAP yield were predicted by central composite design and validated. Bioorganic fertilizer containing 8.46 log(10) ITS copies g(-1) dry weight of SQR-T037 and 1291.73 mg kg(-1) dry weight of 6PAP, and having the highest (p<0.05) biocontrol efficacy, was achieved at 36.7 fermentation days, 25.9°C temperature, 7.6% inoculum content, 41.0% vinegar-production residue, 20.0% rice straw and 39.0% cattle dung. This is a way to offer a high value-added use for agro-industrial wastes. Copyright © 2010 Elsevier Ltd. All rights reserved.

Aspergillus oryzae-based cell factory for direct kojic acid production from cellulose.

PubMed

Yamada, Ryosuke; Yoshie, Toshihide; Wakai, Satoshi; Asai-Nakashima, Nanami; Okazaki, Fumiyoshi; Ogino, Chiaki; Hisada, Hiromoto; Tsutsumi, Hiroko; Hata, Yoji; Kondo, Akihiko

2014-05-18

Kojic acid (5-Hydroxy-2-(hydroxymethyl)-4-pyrone) is one of the major secondary metabolites in Aspergillus oryzae. It is widely used in food, pharmaceuticals, and cosmetics. The production cost, however, is too high for its use in many applications. Thus, an efficient and cost-effective kojic acid production process would be valuable. However, little is known about the complete set of genes for kojic acid production. Currently, kojic acid is produced from glucose. The efficient production of kojic acid using cellulose as an inexpensive substrate would help establish cost-effective kojic acid production. A kojic acid transcription factor gene over-expressing the A. oryzae strain was constructed. Three genes related to kojic acid production in this strain were transcribed in higher amounts than those found in the wild-type strain. This strain produced 26.4 g/L kojic acid from 80 g/L glucose. Furthermore, this strain was transformed with plasmid harboring 3 cellulase genes. The resultant A. oryzae strain successfully produced 0.18 g/L of kojic acid in 6 days of fermentation from the phosphoric acid swollen cellulose. Kojic acid was produced directly from cellulose material using genetically engineered A. oryzae. Because A. oryzae has efficient protein secretion ability and secondary metabolite productivity, an A. oryzae-based cell factory could be a platform for the production of various kinds of bio-based chemicals.

Aspergillus oryzae-based cell factory for direct kojic acid production from cellulose

PubMed Central

2014-01-01

Background Kojic acid (5-Hydroxy-2-(hydroxymethyl)-4-pyrone) is one of the major secondary metabolites in Aspergillus oryzae. It is widely used in food, pharmaceuticals, and cosmetics. The production cost, however, is too high for its use in many applications. Thus, an efficient and cost-effective kojic acid production process would be valuable. However, little is known about the complete set of genes for kojic acid production. Currently, kojic acid is produced from glucose. The efficient production of kojic acid using cellulose as an inexpensive substrate would help establish cost-effective kojic acid production. Results A kojic acid transcription factor gene over-expressing the A. oryzae strain was constructed. Three genes related to kojic acid production in this strain were transcribed in higher amounts than those found in the wild-type strain. This strain produced 26.4 g/L kojic acid from 80 g/L glucose. Furthermore, this strain was transformed with plasmid harboring 3 cellulase genes. The resultant A. oryzae strain successfully produced 0.18 g/L of kojic acid in 6 days of fermentation from the phosphoric acid swollen cellulose. Conclusions Kojic acid was produced directly from cellulose material using genetically engineered A. oryzae. Because A. oryzae has efficient protein secretion ability and secondary metabolite productivity, an A. oryzae-based cell factory could be a platform for the production of various kinds of bio-based chemicals. PMID:24885968

Aspergillus niger contains the cryptic phylogenetic species A. awamori.

PubMed

Perrone, Giancarlo; Stea, Gaetano; Epifani, Filomena; Varga, János; Frisvad, Jens C; Samson, Robert A

2011-11-01

Aspergillus section Nigri is an important group of species for food and medical mycology, and biotechnology. The Aspergillus niger 'aggregate' represents its most complicated taxonomic subgroup containing eight morphologically indistinguishable taxa: A. niger, Aspergillus tubingensis, Aspergillus acidus, Aspergillus brasiliensis, Aspergillus costaricaensis, Aspergillus lacticoffeatus, Aspergillus piperis, and Aspergillus vadensis. Aspergillus awamori, first described by Nakazawa, has been compared taxonomically with other black aspergilli and recently it has been treated as a synonym of A. niger. Phylogenetic analyses of sequences generated from portions of three genes coding for the proteins β-tubulin (benA), calmodulin (CaM), and the translation elongation factor-1 alpha (TEF-1α) of a population of A. niger strains isolated from grapes in Europe revealed the presence of a cryptic phylogenetic species within this population, A. awamori. Morphological, physiological, ecological and chemical data overlap occurred between A. niger and the cryptic A. awamori, however the splitting of these two species was also supported by AFLP analysis of the full genome. Isolates in both phylospecies can produce the mycotoxins ochratoxin A and fumonisin B₂, and they also share the production of pyranonigrin A, tensidol B, funalenone, malformins, and naphtho-γ-pyrones. In addition, sequence analysis of four putative A. awamori strains from Japan, used in the koji industrial fermentation, revealed that none of these strains belong to the A. awamori phylospecies. Copyright © 2011 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Novel nitrogen-fixing Acetobacter nitrogenifigens sp. nov., isolated from Kombucha tea.

PubMed

Dutta, Debasree; Gachhui, Ratan

2006-08-01

The four nitrogen-fixing bacteria so far described in the family Acetobacteraceae belong to the genera Gluconacetobacter and Acetobacter. Nitrogen-fixing bacterial strain RG1(T) was isolated from Kombucha tea and, based on the phylogenetic analysis of 16S rRNA gene sequence which is supported by a high bootstrap value, was found to belong to the genus Acetobacter. Strain RG1(T) differed from Acetobacter aceti, the nearest member with a 16S rRNA gene sequence similarity of 98.2 %, and type strains of other Acetobacter species with regard to several characteristics of growth features in culture media, growth in nitrogen-free medium, production of gamma-pyrone from glucose and dihydroxyacetone from glycerol. Strain RG1(T) utilized maltose, glycerol, sorbitol, fructose, galactose, arabinose and ethanol, but not methanol as a carbon source. These results, along with electrophoretic mobility patterns of nine metabolic enzymes, suggest that strain RG1(T) represents a novel nitrogen-fixing species. The ubiquinone present was Q-9 and DNA G+C content was 64.1 mol%. Strain RG1(T) exhibited a low value of 2-24 % DNA-DNA relatedness to the type strains of related acetobacters, which placed it as a separate taxon. On the basis of this data, the name Acetobacter nitrogenifigens sp. nov. is proposed, with the type strain RG1(T) (=MTCC 6912(T)=LMG 23498(T)).

Pharmacological and Nutritional Effects of Natural Coumarins and Their Structure-Activity Relationships.

PubMed

Zhu, Jing-Jing; Jiang, Jian-Guo

2018-05-11

Coumarins are fused benzene and pyrone ring systems with a wide spectrum of bioactivities including anti-tumor, anti-inflammation, antiviral and antibacterial effects. In this paper, the current development of coumarins-based drugs is introduced, and their structure-activity relationship is discussed by reviewing the relevant literatures published in the past twenty years. Coumarin molecules can be customized by the target site to prevent systemic side effects by virtue of structural modification. The ortho-phenolic hydroxyl on the benzene ring had remarkable antioxidant and anti-tumor activities. Coumarins with aryl groups at the C-4 position have good activities in anti-HIV, anti-tumor, anti-inflammation and analgesia. C-3 phenylcoumarins have strong anti-HIV and antioxidant effects. Tetracycline pyranocoumarins can significantly inhibit the HIV, osthol structural analogues have antimicrobial activity. Praeruptorin C and its derivatives play an important role in lowering blood pressure and dilating coronary arteries, and khellactone derivatives have significant inhibitory effects on AIDS, cancer and cardiovascular diseases. It is concluded that the specific site on the core structure of coumarin exhibits one or more activities due to the electronic or steric effects of the substituents. This review is designed to be conducive to rational design and development of more active and less toxic agents with a coumarin scaffold. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Quality evaluation of Semen Cassiae (Cassia obtusifolia L.) by using ultra-high performance liquid chromatography coupled with mass spectrometry.

PubMed

Zhang, Wei-Dong; Wang, Ying; Wang, Qing; Yang, Wan-Jun; Gu, Yi; Wang, Rong; Song, Xiao-Mei; Wang, Xiao-Juan

2012-08-01

A sensitive and reliable ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry has been developed and partially validated to evaluate the quality of Semen Cassiae (Cassia obtusifolia L.) through simultaneous determination of 11 anthraquinones and two naphtha-γ-pyrone compounds. The analysis was achieved on a Poroshell 120 EC-C(18) column (100 mm × 2.1 mm, 2.7 μm; Agilent, Palo Alto, CA, USA) with gradient elution using a mobile phase that consisted of acetonitrile-water (30 mM ammonium acetate) at a flow rate of 0.4 mL/min. For quantitative analysis, all calibration curves showed perfect linear regression (r(2) > 0.99) within the testing range. This method was also validated with respect to precision and accuracy, and was successfully applied to quantify the 13 components in nine batches of Semen Cassiae samples from different areas. The performance of developed method was compared with that of conventional high-performance liquid chromatography method. The significant advantages of the former include high-speed chromatographic separation, four times faster than high-performance liquid chromatography with conventional columns, and great enhancement in sensitivity. This developed method provided a new basis for overall assessment on quality of Semen Cassiae. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and characterization of two dehydroacetic acid derivatives and molybdenum(V) complexes: an NMR and crystallographic study

NASA Astrophysics Data System (ADS)

Cindrić, Marina; Vrdoljak, Višnja; Kajfež Novak, Tanja; Ćurić, Manda; Brbot-Šaranović, Ana; Kamenar, Boris

2004-09-01

Two enaminones ethyl 4-(4-hydroxy-6-methyl-2 H-pyran-2-on-3-yl)-2-(tryptamino)-4-oxo-2-butenoate ( HL1) and 3-(1-tryptaminoetylidene)-6-methyl-2 H-pyran-2,4(3H)-dione ( HL2) have been prepared by the reactions of tryptamine with 2-hydroxy-4-(4-hydroxy)-6-methyl)-2 Hbb-pyrane-2-on-3-yl)-4-oxo-2-butenoate (ehmpb) or with dehydroacetic acid (dha). The NMR spectroscopy confirmed that both tautomeric forms of HL1: endo-enol (tautomer A with hydroxyl group at position 4) and exo-enol form (tautomer B with hydroxyl group at position 7) are present in the DMSO- d6 solution. The molecular and crystal structure as well as the NMR data of HL2 showed that the condensation of dha and tryptamine occurs at acetyl-carbonyl and not at the pyrone-carbonyl group. Also new dinuclear [Mo 2O 4(L 1) 2(CH 3OH) 2] ( 1) and hexanuclear molybdenum(V) complexes (C 10H 12NH)[Mo 6O 12(OCH 3) 4(acac) 3] ( 2) have been prepared by the reactions of [Mo 2O 3(acac) 4] (acac=acetilacetonate ion) with HL1 or with tryptamine. All compounds have been characterized also by means of elemental analyses, IR spectroscopy as well as by thermal analyses.

A coupled in vitro/in vivo approach for engineering a heterologous type III PKS to enhance polyketide biosynthesis in Saccharomyces cerevisiae.

PubMed

Vickery, Christopher R; Cardenas, Javier; Bowman, Marianne E; Burkart, Michael D; Da Silva, Nancy A; Noel, Joseph P

2018-06-01

Polyketides are attractive compounds for uses ranging from biorenewable chemical precursors to high-value therapeutics. In many cases, synthesis in a heterologous host is required to produce these compounds in industrially relevant quantities. The type III polyketide synthase 2-pyrone synthase (2-PS) from Gerbera hybrida was used for the production of triacetic acid lactone (TAL) in Saccharomyces cerevisiae. Initial in vitro characterization of 2-PS led to the identification of active site variants with improved kinetic properties relative to wildtype. Further in vivo evaluation in S. cerevisiae suggested certain 2-PS mutations altered enzyme stability during fermentation. In vivo experiments also revealed beneficial cysteine to serine mutations that were not initially explored due to their distance from the active site of 2-PS, leading to the design of additional 2-PS enzymes. While these variants showed varying catalytic efficiencies in vitro, they exhibited up to 2.5-fold increases in TAL production when expressed in S. cerevisiae. Coupling of the 2-PS variant [C35S,C372S] to an engineered S. cerevisiae strain led to over 10 g/L TAL at 38% of theoretical yield following fed-batch fermentation, the highest reported to date. Our studies demonstrate the success of a coupled in vitro/in vivo approach to engineering enzymes and provide insight on cysteine-rich enzymes and design principles toward their use in non-native microbial hosts. © 2018 Wiley Periodicals, Inc.

Synthesis and radical scavenging activity of 6-hydroxyl-4-methylcoumarin and its derivatives

NASA Astrophysics Data System (ADS)

Jumal, Juliana; Ayomide, Adetunji Fridaos

2018-06-01

Four compounds of coumarin derivatives namely 6-hydroxyl-4-methylcoumarin (I), 6-hydroxyl-4-methyl-5-(p-nitrophenyl azocoumarin) (II), 6-hydroxyl-4-methyl-5,7-(bis-p-nitrophenyl azocoumarin) (III) and 6-hydroxyl-4-methyl-5,7-(bis-p-chlorophenyl azocoumarin) (IV) were successfully synthesized. These compounds were prepared by reacting hydroquinone with ethylacetoacetate and selected anilines which are chloro and nitro aniline. All synthesized compounds were characterized by CHN micro-elemental analysis, 1H Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared (FTIR) spectroscopic methods. The infrared spectra of these compounds exhibited five important stretching vibrations: ʋ(-OH), ʋ(C=O), ʋ(C=C), ʋ(C-O) and ʋ(C-N) at 3441-3359 cm-1, 1604-1632 cm-1, 1581-1496 cm-1, 1331-1225 cm-1, 1251-1109 cm-1, respectively. 1H NMR spectra of these compounds show the presence of proton aromatic, proton methyl and proton pyrone ring with the chemical shift at δH 7.00-8.70 ppm, δH 2.20-2.50 ppm and δH 6.10-6.90 ppm, respectively. CHN analysis results of all compounds are in good agreement with the calculated values. All the synthesized compounds were evaluated for their antioxidant activity using DPPH method and ascorbic acid used as the standard. UV-Vis spectroscopic technique was used to investigate the absorbance of these compounds. Compound (II) shows high antioxidant activities compared to compound (I), (III) and (IV) which show moderate to low activities.

Functional Chemical Groups that May Likely Become a Source for the Synthesis of Novel Central Nervous System (CNS) Acting Drugs.

PubMed

Saganuwan, Saganuwan A

2017-01-01

Central Nervous System (CNS) disorders are on increase perhaps due to genetic, enviromental, social and dietetic factors. Unfortunately, a large number of CNS drugs have adverse effects such as addiction, tolerance, psychological and physical dependence. In view of this, literature search was carried out with a view to identify functional chemical groups that may serve as lead molecules for synthesis of compounds that may have CNS activity. The search revealed that heterocycles that have heteroatoms such as nitrogen (N), sulphur (S) and oxygen (O) form the largest class of organic compounds. They replace carbon in a benzene ring to form pyridine. Compounds with furan, thiophene, pyrrole, pyridine, azole, imidazole, indole, purine, pyrimidine, esters, carboxylic acid, aldehyde, pyrylium, pyrone, pyrodine, barbituric acid, barbiturate, quinoline, quinolone, isoquinolone, coumarin, alkylpyridine, picoline, piperidine, diazine, carboxamide, flavonoid glycoside, oxindole, aminophenol, benzimidazole, benzoxazole, benzothiazole, and chromone chemical groups among others may have CNS effects ranging from depression passing through euphoria to convulsion. Examples of the compounds with the functional groups include but not limited to coal tar, pyridostigmine, pralidoxime, quinine, mefloquine, pyrilamine, pyronaridine, ciprofloxacin and piroxicam. A number of them can undergo keto-enol tautomerism. Chiral amines may be used for derivation of chiral carboxylic acids which are components of tautomers. Some tautomers may cause parkinsonism and Stevens Johnson syndrome. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Bioactive metabolites from the endophytic fungus Ampelomyces sp. isolated from the medicinal plant Urospermum picroides.

PubMed

Aly, Amal H; Edrada-Ebel, Ruangelie; Wray, Victor; Müller, Werner E G; Kozytska, Svitlana; Hentschel, Ute; Proksch, Peter; Ebel, Rainer

2008-05-01

Extracts of cultures grown in liquid or on solid rice media of the fungal endophyte Ampelomyces sp. isolated from the medicinal plant Urospermum picroides exhibited considerable cytotoxic activity when tested in vitro against L5178Y cells. Chromatographic separation yielded 14 natural products that were unequivocally identified based on their 1H and 13C NMR as well as mass spectra and comparison with previously published data. Six compounds (2, 4, 5, 7, 9 and 11) were natural products. Both fungal extracts differed considerably in their secondary metabolites. The extract obtained from liquid cultures afforded a pyrone (2) and sulfated anthraquinones (7 and 9) along with the known compounds 1, 3, 6 and 8. When grown on solid rice medium the fungus yielded three compounds 4, 5 and 11 in addition to several known metabolites including 6, 8, 10, 12, 13 and 14. Compounds 4, 8 and 10 showed the strongest cytotoxic activity against L5178Y cells with EC50 values ranging from 0.2-7.3microg/ml. Furthermore, 8 and 10 displayed antimicrobial activity against the Gram-positive pathogens, Staphylococcus aureus, S. epidermidis and Enterococcus faecalis at minimal inhibitory concentrations (MIC) of 12.5microg/ml and 12.5-25microg/ml, respectively. Interestingly, 6 and 8 were also identified as constituents of an extract derived from a healthy plant sample of the host plant U. picroides thereby indicating that the production of bioactive natural products by the endophyte proceeds also under in situ conditions within the host plant.

Impact of competitive fungi on Trichothecene production by Fusarium graminearum.

PubMed

Cooney, J M; Lauren, D R; di Menna, M E

2001-01-01

Bioassays were used to determine the production of the trichothecene mycotoxin, deoxynivalenol (DON), by two isolates of Fusarium graminearum when grown in association with potentially competitive fungi and an antifungal chemical, 6-pentyl-alpha-pyrone (6PAP). The presence of 6PAP in the culture medium reduced DON production by as much as 80%, but this effect was reduced for the F. graminearum isolate that most efficiently metabolized the added 6PAP. A 6PAP-producing Trichoderma isolate grown in a competition assay system with the F. graminearum isolates was also able to substantially reduce DON production. When Fusarium isolates (F. crookwellense, F. culmorum, F. subglutinans, F. poae, F. equiseti, F. avenaceum, and F. sambucinum), which co-occur with F. graminearum in New Zealand maize plants (Zea mays), were grown in competition assays, the effect on DON production was variable. However, all isolates of F. subglutinans tested were shown to cause reductions in DON production (by 13-76%, mean = 62%). F. subglutinans frequently co-occurs with F. graminearum, but its presence can vary with location and time of the season. When the competitive fungus tested was also a trichothecene producer (e.g., of nivalenol), both toxins were produced in the assay medium. The results indicate that mycotoxin production by F. graminearum can be affected by the presence of particular competitive fungi. These results have implications for an ecological understanding of pathogenicity and of mycotoxin accumulation in plants. Early establishment of F. subglutinans, for example, may act as a biological control mechanism providing a temporary protection against invasion by more commonly toxigenic fusaria such as F. graminearum.

Protective role of arzanol against lipid peroxidation in biological systems.

PubMed

Rosa, Antonella; Pollastro, Federica; Atzeri, Angela; Appendino, Giovanni; Melis, M Paola; Deiana, Monica; Incani, Alessandra; Loru, Debora; Dessì, M Assunta

2011-01-01

This study examines the protective effect of arzanol, a pyrone-phloroglucinol etherodimer from Helichrysum italicum subsp. microphyllum, against the oxidative modification of lipid components induced by Cu(2+) ions in human low density lipoprotein (LDL) and by tert-butyl hydroperoxide (TBH) in cell membranes. LDL pre-treatment with arzanol significantly preserved lipoproteins from oxidative damage at 2h of oxidation, and showed a remarkable protective effect on the reduction of polyunsaturated fatty acids and cholesterol levels, inhibiting the increase of oxidative products (conjugated dienes fatty acids hydroperoxides, 7β-hydroxycholesterol, and 7-ketocholesterol). Arzanol, at non-cytotoxic concentrations, exerted a noteworthy protection on TBH-induced oxidative damage in a line of fibroblasts derived from monkey kidney (Vero cells) and in human intestinal epithelial cells (Caco-2), decreasing, in both cell lines, the formation of oxidative products (hydroperoxides and 7-ketocholesterol) from the degradation of unsaturated fatty acids and cholesterol. The cellular uptake and transepithelial transport of the compound were also investigated in Caco-2 cell monolayers. Arzanol appeared to accumulate in Caco-2 epithelial cells. This phenol was able to pass through the intestinal Caco-2 monolayers, the apparent permeability coefficients (P(app)) in the apical-to-basolateral and basolateral-to-apical direction at 2h were 1.93±0.36×10(-5) and 2.20±0.004×10(-5)cm/s, respectively, suggesting a passive diffusion pathway. The results of the work qualify arzanol as a potent natural antioxidant with a protective effect against lipid oxidation in biological systems. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Regiochemistry in cobalt-mediated intermolecular Pauson-Khand reactions of unsymmetrical internal heteroaromatic alkynes with norbornene.

PubMed

Moulton, Benjamin E; Whitwood, Adrian C; Duhme-Klair, Anne K; Lynam, Jason M; Fairlamb, Ian J S

2011-07-01

The intermolecular Pauson-Khand (PK) reactions of sterically comparable (2-phenylethynyl)heteroaromatic compounds with norbornene, mediated by Co(2)(CO)(8) to give cyclopentenone products, were examined in this study. A synthetic protocol utilizing focused-microwave dielectric heating proved indispensable in the efficient synthesis of the PK cyclopentenone products. "π-Deficient" heteroaromatic substrates, e.g., 2-pyrones, and some "π-excessive" heteroaromatics such as 2- and 3-thiophene and 2-furan favor the β-position in the newly formed cyclopentenone ring. Other π-excessive heteroaromatics such as 2-pyrrole or 2-indole favor the α-position. A π-excessive 3-indole derivative gave a nearly equal mixture of regioisomers. The position of the nitrogen in pyridyl-containing alkyne substrates also affects the regiochemical outcome of the PK reaction. A 2-pyridyl alkyne, possessing a proximal nitrogen, influences the regioselectivity relative to a 4-pyridyl variant quite dramatically, favoring the β-position in the newly formed cyclopentenone ring. A 2-pyrimidylalkyne exhibits similar behavior to the 2-pyridylalkyne. Compounds that do not participate in PK reactions with norbornene include (2-phenylethynyl)imidazoles and the related benzimidazoles, which promote rapid decomposition of the in situ generated (μ(2)-alkyne)Co(2)(CO)(6) complexes. This stands in contrast with other nitrogen-containing heteroaromatics, e.g., pyrrole-, indole-, and pyrimidine-derived compounds, which effectively undergo PK reactions. Overall, the type of heteroaromatic group dramatically influences PK regioselectivity, which can in part be explained by rationalization of the current reaction mechanism, but not fully.

Simultaneous qualitative and quantitative determination of phenolic compounds in Aloe barbadensis Mill by liquid chromatography-mass spectrometry-ion trap-time-of-flight and high performance liquid chromatography-diode array detector.

PubMed

Wu, Xiaofang; Ding, Wenjing; Zhong, Jiasheng; Wan, Jinzhi; Xie, Zhiyong

2013-06-01

An effective and comprehensive method was developed for the simultaneous analysis of phenolic compounds in the dried exudate of Aloe barbadensis Mill by liquid chromatography-mass spectrometry-ion trap-time-of-flight (LCMS-IT-TOF) and high performance liquid chromatography-diode array detector (HPLC-DAD). Qualitative analysis of all the compounds presented in A. barbadensis Mill was performed on LCMS-IT-TOF, and the diagnostic fragmentation patterns of different types of phenolic compounds (chromones, phenyl pyrones, naphthalene derivative, anthrones and anthraquinones) were discussed on the basis of ESI-IT-TOF MS of components in A. barbadensis Mill and eleven authentic standards. Under the optimal HPLC-DAD chromatographic conditions, quantification of 11 typical phenolic compounds in 15 batches of A. barbadensis Mill was achieved on an Agilent TC-C18 column using gradient elution with a solvent system of methanol and water at a flow rate of 1.0mLmin(-1) and detected at 230nm. All calibration curves exhibited good linear relationship (r(2)>0.9991). The relative standard deviation values for intraday precision were less than 2% with accuracies between 98.21% and 104.57%. The recoveries of the eleven analytes ranged from 97.53 to 105.00% with RSDs less than 2%. This is the first simultaneous characterization and quantitative determination of multiple phenolic compounds in A. barbadensis Mill from locally grown cultivars in China by LCMS-IT-TOF and HPLC-DAD, which can be applied to standardize the quality of A. barbadensis Mill and the future design of nutraceutical and cosmetic preparations. Copyright © 2013 Elsevier B.V. All rights reserved.

Structure and catalytic mechanism of LigI: insight into the amidohydrolase enzymes of cog3618 and lignin degradation.

PubMed

Hobbs, Merlin Eric; Malashkevich, Vladimir; Williams, Howard J; Xu, Chengfu; Sauder, J Michael; Burley, Stephen K; Almo, Steven C; Raushel, Frank M

2012-04-24

LigI from Sphingomonas paucimobilis catalyzes the reversible hydrolysis of 2-pyrone-4,6-dicarboxylate (PDC) to 4-oxalomesaconate and 4-carboxy-2-hydroxymuconate in the degradation of lignin. This protein is a member of the amidohydrolase superfamily of enzymes. The protein was expressed in Escherichia coli and then purified to homogeneity. The purified recombinant enzyme does not contain bound metal ions, and the addition of metal chelators or divalent metal ions to the assay mixtures does not affect the rate of product formation. This is the first enzyme from the amidohydrolase superfamily that does not require a divalent metal ion for catalytic activity. The kinetic constants for the hydrolysis of PDC are 340 s(-1) and 9.8 × 10(6) M(-1) s(-1) (k(cat) and k(cat)/K(m), respectively). The pH dependence on the kinetic constants suggests that a single active site residue must be deprotonated for the hydrolysis of PDC. The site of nucleophilic attack was determined by conducting the hydrolysis of PDC in (18)O-labeled water and subsequent (13)C nuclear magnetic resonance analysis. The crystal structures of wild-type LigI and the D248A mutant in the presence of the reaction product were determined to a resolution of 1.9 Å. The C-8 and C-11 carboxylate groups of PDC are coordinated within the active site via ion pair interactions with Arg-130 and Arg-124, respectively. The hydrolytic water molecule is activated by the transfer of a proton to Asp-248. The carbonyl group of the lactone substrate is activated by electrostatic interactions with His-180, His-31, and His-33.

Tuning the Electronic Structure of Fe(II) Polypyridines via Donor Atom and Ligand Scaffold Modifications: A Computational Study.

PubMed

Bowman, David N; Bondarev, Alexey; Mukherjee, Sriparna; Jakubikova, Elena

2015-09-08

Fe(II) polypyridines are an important class of pseudo-octahedral metal complexes known for their potential applications in molecular electronic switches, data storage and display devices, sensors, and dye-sensitized solar cells. Fe(II) polypyridines have a d(6) electronic configuration and pseudo-octahedral geometry and can therefore possess either a high-spin (quintet) or a low-spin (singlet) ground state. In this study, we investigate a series of complexes based on [Fe(tpy)2](2+) (tpy = 2,2';6',2″-terpyridine) and [Fe(dcpp)2](2+) (dcpp = 2,6-bis(2-carboxypyridyl)pyridine). The ligand field strength in these complexes is systematically tuned by replacing the central pyridine with five-membered (N-heterocyclic carbene, pyrrole, furan) or six-membered (aryl, thiazine-1,1-dioxide, 4-pyrone) moieties. To determine the impact of ligand substitutions on the relative energies of metal-centered states, the singlet, triplet, and quintet states of the Fe(II) complexes were optimized in water (PCM) using density functional theory at the B3LYP+D2 level with 6-311G* (nonmetals) and SDD (Fe) basis sets. It was found that the dcpp ligand scaffold allows for a more ideal octahedral coordination environment in comparison to the tpy ligand scaffold. The presence of six-membered central rings also allows for a more ideally octahedral coordination environment relative to five-membered central rings, regardless of the ligand scaffold. We find that the ligand field strength in the Fe(II) polypyridines can be tuned by altering the donor atom identity, with C donor atoms providing the strongest ligand field.

New natural products isolated from Metarhizium robertsii ARSEF 23 by chemical screening and identification of the gene cluster through engineered biosynthesis in Aspergillus nidulans A1145.

PubMed

Kato, Hiroki; Tsunematsu, Yuta; Yamamoto, Tsuyoshi; Namiki, Takuya; Kishimoto, Shinji; Noguchi, Hiroshi; Watanabe, Kenji

2016-07-01

To rapidly identify novel natural products and their associated biosynthetic genes from underutilized and genetically difficult-to-manipulate microbes, we developed a method that uses (1) chemical screening to isolate novel microbial secondary metabolites, (2) bioinformatic analyses to identify a potential biosynthetic gene cluster and (3) heterologous expression of the genes in a convenient host to confirm the identity of the gene cluster and the proposed biosynthetic mechanism. The chemical screen was achieved by searching known natural product databases with data from liquid chromatographic and high-resolution mass spectrometric analyses collected on the extract from a target microbe culture. Using this method, we were able to isolate two new meroterpenes, subglutinols C (1) and D (2), from an entomopathogenic filamentous fungus Metarhizium robertsii ARSEF 23. Bioinformatics analysis of the genome allowed us to identify a gene cluster likely to be responsible for the formation of subglutinols. Heterologous expression of three genes from the gene cluster encoding a polyketide synthase, a prenyltransferase and a geranylgeranyl pyrophosphate synthase in Aspergillus nidulans A1145 afforded an α-pyrone-fused uncyclized diterpene, the expected intermediate of the subglutinol biosynthesis, thereby confirming the gene cluster to be responsible for the subglutinol biosynthesis. These results indicate the usefulness of our methodology in isolating new natural products and identifying their associated biosynthetic gene cluster from microbes that are not amenable to genetic manipulation. Our method should facilitate the natural product discovery efforts by expediting the identification of new secondary metabolites and their associated biosynthetic genes from a wider source of microbes.

Sublethal effects in Perinereis gualpensis (Polychaeta: Nereididae) exposed to mercury-pyrene sediment mixture observed in a multipolluted estuary.

PubMed

Díaz-Jaramillo, M; Miglioranza, K S B; Carriquiriborde, P; Marino, D; Pegoraro, C N; Valenzuela, G; Barra, R

2017-08-01

Sediment-living organisms can be subjected to a multi-pollution condition due to an increase in the diversity of contaminants. Sediment mixtures of Mercury (Hg) and some polycyclic aromatics hydrocarbons like Pyrene (Pyr) are common in heavily industrialized coastal zones. In the present study, greater than (>) and less than (<) probable effect concentration levels (PELs) of Hg and Pyr were assessed using spiked sediments in order to determine combined (Hg + Pyr) effects in uptake, metabolization and oxidative balance in the polychaete Perinereis gualpensis at short and medium-term exposure. Hg + Pyr significantly influenced the uptake/kinetics of Hg and Pyr metabolite 1-OH-pyrene in polychaete tissues during the exposure time compared with separate treatments of each analyte (p < 0.05). Both the Hg-only and Pyr-only exposures significantly influenced both enzymatic and non-enzymatic responses respect to control groups (p < 0.05). The Hg-only treatment showed the worst scenario related to the activation and subsequent inhibition of glutathione S- transferase (GST) and peroxidase (GPx) activities, high levels of Thiol-groups (SH-groups), low antioxidant capacity (ACAP) and enhanced lipid peroxidation (TBARS) in the last days of exposure (p < 0.05). In contrast, ragworms exposed to Hg + Pyr showed a significant increase in both enzymatic and non-enzymatic activity during the first days of exposure and the absence of lipid peroxidation during the whole experiment. Our results suggest different oxidative stress scenarios in P. gualpensis when exposed to >PEL Hg concentration with

Production and characterization of bioactive metabolites from piezotolerant deep sea fungus Nigrospora sp. in submerged fermentation.

PubMed

Arumugam, G K; Srinivasan, S K; Joshi, G; Gopal, D; Ramalingam, K

2015-01-01

To produce and characterize bioactive metabolites from piezotolerant marine fungus Nigrospora sp. in submerged fermentation. A distinct marine strain, Nigrospora sp. NIOT has been isolated from a depth of 800 m at the Arabian Sea. The 18S rRNA and internal transcribed spacers (ITS) analysis demonstrates its close association with the genus Nigrospora. Effect of pH, temperature, salinity, carbon source and amino acids was studied to optimize the fermentation conditions. Optimal mycelia growth and secondary metabolites production were observed at 6·0-8·0 pH, 20-30°C temperature, 7·5% salinity, sucrose as carbon source and tryptophan as amino acid source. The extracellular secondary metabolites exhibited high antimicrobial activities against both gram-positive and gram-negative pathogenic bacteria with minimal inhibitory concentration (MIC) values higher than 30 μg ml(-1). Strongest cytotoxicity was observed in all cell lines tested, GI50 (growth inhibition by 50%) was calculated to be 1·35, 3·2, 0·13 and 0·35 μg ml(-1) against U937, MCF-7, A673 and Jurkat, respectively. Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GC-MS) analyses of secondary metabolites confirmed the production of antimicrobial and anticancer substances. A piezotolerant fungus Nigrospora sp. NIOT isolated from deep sea environment was successfully cultured under submerged fermentation. The secondary metabolites produced from this organism showed potent antimicrobial and anticancer activities with immediate application to cosmetics and pharmaceutical industries. This is the first study exploring Nigrospora sp. from 800 m in marine environment. This deep sea fungus under optimized culture conditions effectively produced bioactive secondary metabolites such as griseofulvin, spirobenzofuran and pyrone derivatives at higher concentrations. © 2014 The Society for Applied Microbiology.

Fatty acid ethyl ester synthase inhibition ameliorates ethanol-induced Ca2+-dependent mitochondrial dysfunction and acute pancreatitis

PubMed Central

Huang, Wei; Booth, David M; Cane, Matthew C; Chvanov, Michael; Javed, Muhammad A; Elliott, Victoria L; Armstrong, Jane A; Dingsdale, Hayley; Cash, Nicole; Li, Yan; Greenhalf, William; Mukherjee, Rajarshi; Kaphalia, Bhupendra S; Jaffar, Mohammed; Petersen, Ole H; Tepikin, Alexei V; Sutton, Robert; Criddle, David N

2014-01-01

Objective Non-oxidative metabolism of ethanol (NOME) produces fatty acid ethyl esters (FAEEs) via carboxylester lipase (CEL) and other enzyme action implicated in mitochondrial injury and acute pancreatitis (AP). This study investigated the relative importance of oxidative and non-oxidative pathways in mitochondrial dysfunction, pancreatic damage and development of alcoholic AP, and whether deleterious effects of NOME are preventable. Design Intracellular calcium ([Ca2+]C), NAD(P)H, mitochondrial membrane potential and activation of apoptotic and necrotic cell death pathways were examined in isolated pancreatic acinar cells in response to ethanol and/or palmitoleic acid (POA) in the presence or absence of 4-methylpyrazole (4-MP) to inhibit oxidative metabolism. A novel in vivo model of alcoholic AP induced by intraperitoneal administration of ethanol and POA was developed to assess the effects of manipulating alcohol metabolism. Results Inhibition of OME with 4-MP converted predominantly transient [Ca2+]C rises induced by low ethanol/POA combination to sustained elevations, with concurrent mitochondrial depolarisation, fall of NAD(P)H and cellular necrosis in vitro. All effects were prevented by 3-benzyl-6-chloro-2-pyrone (3-BCP), a CEL inhibitor. 3-BCP also significantly inhibited rises of pancreatic FAEE in vivo and ameliorated acute pancreatic damage and inflammation induced by administration of ethanol and POA to mice. Conclusions A combination of low ethanol and fatty acid that did not exert deleterious effects per se became toxic when oxidative metabolism was inhibited. The in vitro and in vivo damage was markedly inhibited by blockade of CEL, indicating the potential for development of specific therapy for treatment of alcoholic AP via inhibition of FAEE generation. PMID:24162590

A Large-Scale Genetic Screen in Arabidopsis to Identify Genes Involved in Pollen Exine Production1[C][W][OA

PubMed Central

Dobritsa, Anna A.; Geanconteri, Aliza; Shrestha, Jay; Carlson, Ann; Kooyers, Nicholas; Coerper, Daniel; Urbanczyk-Wochniak, Ewa; Bench, Bennie J.; Sumner, Lloyd W.; Swanson, Robert; Preuss, Daphne

2011-01-01

Exine, the outer plant pollen wall, has elaborate species-specific patterns, provides a protective barrier for male gametophytes, and serves as a mediator of strong and species-specific pollen-stigma adhesion. Exine is made of sporopollenin, a material remarkable for its strength, elasticity, and chemical durability. The chemical nature of sporopollenin, as well as the developmental mechanisms that govern its assembly into diverse patterns in different species, are poorly understood. Here, we describe a simple yet effective genetic screen in Arabidopsis (Arabidopsis thaliana) that was undertaken to advance our understanding of sporopollenin synthesis and exine assembly. This screen led to the recovery of mutants with a variety of defects in exine structure, including multiple mutants with novel phenotypes. Fifty-six mutants were selected for further characterization and are reported here. In 14 cases, we have mapped defects to specific genes, including four with previously demonstrated or suggested roles in exine development (MALE STERILITY2, CYP703A2, ANTHER-SPECIFIC PROTEIN6, TETRAKETIDE α-PYRONE REDUCTASE/DIHYDROFLAVONOL-4-REDUCTASE-LIKE1), and a number of genes that have not been implicated in exine production prior to this screen (among them, fatty acid ω-hydroxylase CYP704B1, putative glycosyl transferases At1g27600 and At1g33430, 4-coumarate-coenzyme A ligase 4CL3, polygalacturonase QUARTET3, novel gene At5g58100, and nucleotide-sugar transporter At5g65000). Our study illustrates that morphological screens of pollen can be extremely fruitful in identifying previously unknown exine genes and lays the foundation for biochemical, developmental, and evolutionary studies of exine production. PMID:21849515

Plant polyketide synthases: a chalcone synthase-type enzyme which performs a condensation reaction with methylmalonyl-CoA in the biosynthesis of C-methylated chalcones.

PubMed

Schröder, J; Raiber, S; Berger, T; Schmidt, A; Schmidt, J; Soares-Sello, A M; Bardshiri, E; Strack, D; Simpson, T J; Veit, M; Schröder, G

1998-06-09

Heterologous screening of a cDNA library from Pinusstrobus seedlings identified clones for two chalcone synthase (CHS) related proteins (PStrCHS1 and PStrCHS2, 87.6% identity). Heterologous expression in Escherichia coli showed that PStrCHS1 performed the typical CHS reaction, that it used starter CoA-esters from the phenylpropanoid pathway, and that it performed three condensation reactions with malonyl-CoA, followed by the ring closure to the chalcone. PstrCHS2 was completely inactive with these starters and also with linear CoA-esters. Activity was detected only with a diketide derivative (N-acetylcysteamine thioester of 3-oxo-5-phenylpent-4-enoic acid) that corresponded to the CHS reaction intermediate postulated after the first condensation reaction. PstrCHS2 performed only one condensation, with 6-styryl-4-hydroxy-2-pyrone derivatives as release products. The enzyme preferred methylmalonyl-CoA against malonyl-CoA, if only methylmalonyl-CoA was available. These properties and a comparison with the CHS from Pinus sylvestris suggested for PstrCHS2 a special function in the biosynthesis of secondary products. In contrast to P. sylvestris, P. strobus contains C-methylated chalcone derivatives, and the methyl group is at the position predicted from a chain extension with methylmalonyl-CoA in the second condensation of the biosynthetic reaction sequence. We propose that PstrCHS2 specifically contributes the condensing reaction with methylmalonyl-CoA to yield a methylated triketide intermediate. We discuss a model that the biosynthesis of C-methylated chalcones represents the simplest example of a modular polyketide synthase.

HARNESSING THE CHEMISTRY OF CO2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Louie, Janis

2010-05-11

Our research program is broadly focused on activating CO{sub 2} through the use of organic and organometallic based catalysts. Some of our methods have centered on annulation reactions of unsaturated hydrocarbons (and carbonyl substrates) to provide a diverse array of carbocycles and heterocycles. We use a combination of catalyst discovery and optimization in conjunction with classical physical organic chemistry to elucidate the key mechanistic features of the cycloaddition reactions such that the next big advances in catalyst development can be made. Key to all of our cycloaddition reactions is the use of a sterically hindered, electron donating N heterocyclic carbenemore » (NHC) ligand, namely IPr (or SIPr), in conjunction with a low valent nickel pre-catalyst. The efficacy of this ligand is two-fold: (1) the high {delta}-donating ability of the NHC increases the nucleophilicity of the metal center which thereby facilitates interaction with the electrophilic carbonyl and (2) the steric hindrance prevents an otherwise competitive side reaction involving only the alkyne substrate. Such a system has allowed for the facile cycloaddition to prepare highly functionalized pyrones, pyridones, pyrans, as well as novel carbocycles. Importantly, all reactions proceed under extremely mild conditions (room temperature, atmospheric pressures, and short reaction times), require only catalytic amounts of Ni/NHC and readily available starting materials, and afford annulated products in excellent yields. Our current focus revolves around understanding the fundamental processes that govern these cycloadditions such that the next big advance in the cyclization chemistry of CO{sub 2} can be made. Concurrent to our annulation chemistry is our investigation of the potential for imidazolylidenes to function as thermally-actuated CO{sub 2} sequestering and delivery agents.« less

Challenges in identifying sites climatically matched to the native ranges of animal invaders.

PubMed

Rodda, Gordon H; Jarnevich, Catherine S; Reed, Robert N

2011-02-09

Species distribution models are often used to characterize a species' native range climate, so as to identify sites elsewhere in the world that may be climatically similar and therefore at risk of invasion by the species. This endeavor provoked intense public controversy over recent attempts to model areas at risk of invasion by the Indian Python (Python molurus). We evaluated a number of MaxEnt models on this species to assess MaxEnt's utility for vertebrate climate matching. Overall, we found MaxEnt models to be very sensitive to modeling choices and selection of input localities and background regions. As used, MaxEnt invoked minimal protections against data dredging, multi-collinearity of explanatory axes, and overfitting. As used, MaxEnt endeavored to identify a single ideal climate, whereas different climatic considerations may determine range boundaries in different parts of the native range. MaxEnt was extremely sensitive to both the choice of background locations for the python, and to selection of presence points: inclusion of just four erroneous localities was responsible for Pyron et al.'s conclusion that no additional portions of the U.S. mainland were at risk of python invasion. When used with default settings, MaxEnt overfit the realized climate space, identifying models with about 60 parameters, about five times the number of parameters justifiable when optimized on the basis of Akaike's Information Criterion. When used with default settings, MaxEnt may not be an appropriate vehicle for identifying all sites at risk of colonization. Model instability and dearth of protections against overfitting, multi-collinearity, and data dredging may combine with a failure to distinguish fundamental from realized climate envelopes to produce models of limited utility. A priori identification of biologically realistic model structure, combined with computational protections against these statistical problems, may produce more robust models of invasion risk.

Challenges in Identifying Sites Climatically Matched to the Native Ranges of Animal Invaders

PubMed Central

Rodda, Gordon H.; Jarnevich, Catherine S.; Reed, Robert N.

2011-01-01

Background Species distribution models are often used to characterize a species' native range climate, so as to identify sites elsewhere in the world that may be climatically similar and therefore at risk of invasion by the species. This endeavor provoked intense public controversy over recent attempts to model areas at risk of invasion by the Indian Python (Python molurus). We evaluated a number of MaxEnt models on this species to assess MaxEnt's utility for vertebrate climate matching. Methodology/Principal Findings Overall, we found MaxEnt models to be very sensitive to modeling choices and selection of input localities and background regions. As used, MaxEnt invoked minimal protections against data dredging, multi-collinearity of explanatory axes, and overfitting. As used, MaxEnt endeavored to identify a single ideal climate, whereas different climatic considerations may determine range boundaries in different parts of the native range. MaxEnt was extremely sensitive to both the choice of background locations for the python, and to selection of presence points: inclusion of just four erroneous localities was responsible for Pyron et al.'s conclusion that no additional portions of the U.S. mainland were at risk of python invasion. When used with default settings, MaxEnt overfit the realized climate space, identifying models with about 60 parameters, about five times the number of parameters justifiable when optimized on the basis of Akaike's Information Criterion. Conclusions/Significance When used with default settings, MaxEnt may not be an appropriate vehicle for identifying all sites at risk of colonization. Model instability and dearth of protections against overfitting, multi-collinearity, and data dredging may combine with a failure to distinguish fundamental from realized climate envelopes to produce models of limited utility. A priori identification of biologically realistic model structure, combined with computational protections against these statistical problems, may produce more robust models of invasion risk. PMID:21347411

Challenges in identifying sites climatically matched to the native ranges of animal invaders

USGS Publications Warehouse

Rodda, G.H.; Jarnevich, C.S.; Reed, R.N.

2011-01-01

Background: Species distribution models are often used to characterize a species' native range climate, so as to identify sites elsewhere in the world that may be climatically similar and therefore at risk of invasion by the species. This endeavor provoked intense public controversy over recent attempts to model areas at risk of invasion by the Indian Python (Python molurus). We evaluated a number of MaxEnt models on this species to assess MaxEnt's utility for vertebrate climate matching. Methodology/Principal Findings: Overall, we found MaxEnt models to be very sensitive to modeling choices and selection of input localities and background regions. As used, MaxEnt invoked minimal protections against data dredging, multi-collinearity of explanatory axes, and overfitting. As used, MaxEnt endeavored to identify a single ideal climate, whereas different climatic considerations may determine range boundaries in different parts of the native range. MaxEnt was extremely sensitive to both the choice of background locations for the python, and to selection of presence points: inclusion of just four erroneous localities was responsible for Pyron et al.'s conclusion that no additional portions of the U.S. mainland were at risk of python invasion. When used with default settings, MaxEnt overfit the realized climate space, identifying models with about 60 parameters, about five times the number of parameters justifiable when optimized on the basis of Akaike's Information Criterion. Conclusions/Significance: When used with default settings, MaxEnt may not be an appropriate vehicle for identifying all sites at risk of colonization. Model instability and dearth of protections against overfitting, multi-collinearity, and data dredging may combine with a failure to distinguish fundamental from realized climate envelopes to produce models of limited utility. A priori identification of biologically realistic model structure, combined with computational protections against these statistical problems, may produce more robust models of invasion risk.

Ferric maltol is effective in correcting iron deficiency anemia in patients with inflammatory bowel disease: results from a phase-3 clinical trial program.

PubMed

Gasche, Christoph; Ahmad, Tariq; Tulassay, Zsolt; Baumgart, Daniel C; Bokemeyer, Bernd; Büning, Carsten; Howaldt, Stefanie; Stallmach, Andreas

2015-03-01

Iron deficiency anemia (IDA) is frequently seen in inflammatory bowel disease. Traditionally, oral iron supplementation is linked to extensive gastrointestinal side effects and possible disease exacerbation. This multicenter phase-3 study tested the efficacy and safety of ferric maltol, a complex of ferric (Fe) iron with maltol (3-hydroxy-2-methyl-4-pyrone), as a novel oral iron therapy for IDA. Adult patients with quiescent or mild-to-moderate ulcerative colitis or Crohn's disease, mild-to-moderate IDA (9.5-12.0 g/dL and 9.5-13.0 g/dL in females and males, respectively), and documented failure on previous oral ferrous products received oral ferric maltol capsules (30 mg twice a day) or identical placebo for 12 weeks according to a randomized, double-blind, placebo-controlled study design. The primary efficacy endpoint was change in hemoglobin (Hb) from baseline to week 12. Safety and tolerability were assessed. Of 329 patients screened, 128 received randomized therapy (64 ferric maltol-treated and 64 placebo-treated patients) and comprised the intent-to-treat efficacy analysis: 55 ferric maltol patients (86%) and 53 placebo patients (83%) completed the trial. Significant improvements in Hb were observed with ferric maltol versus placebo at weeks 4, 8, and 12: mean (SE) 1.04 (0.11) g/dL, 1.76 (0.15) g/dL, and 2.25 (0.19) g/dL, respectively (P < 0.0001 at all time-points; analysis of covariance). Hb was normalized in two-thirds of patients by week 12. The safety profile of ferric maltol was comparable with placebo, with no impact on inflammatory bowel disease severity. Ferric maltol provided rapid clinically meaningful improvements in Hb and showed a favorable safety profile, suggesting its possible use as an alternative to intravenous iron in IDA inflammatory bowel disease.

Advances in quantum and molecular mechanical (QM/MM) simulations for organic and enzymatic reactions.

PubMed

Acevedo, Orlando; Jorgensen, William L

2010-01-19

Application of combined quantum and molecular mechanical (QM/MM) methods focuses on predicting activation barriers and the structures of stationary points for organic and enzymatic reactions. Characterization of the factors that stabilize transition structures in solution and in enzyme active sites provides a basis for design and optimization of catalysts. Continued technological advances allowed for expansion from prototypical cases to mechanistic studies featuring detailed enzyme and condensed-phase environments with full integration of the QM calculations and configurational sampling. This required improved algorithms featuring fast QM methods, advances in computing changes in free energies including free-energy perturbation (FEP) calculations, and enhanced configurational sampling. In particular, the present Account highlights development of the PDDG/PM3 semi-empirical QM method, computation of multi-dimensional potentials of mean force (PMF), incorporation of on-the-fly QM in Monte Carlo (MC) simulations, and a polynomial quadrature method for efficient modeling of proton-transfer reactions. The utility of this QM/MM/MC/FEP methodology is illustrated for a variety of organic reactions including substitution, decarboxylation, elimination, and pericyclic reactions. A comparison to experimental kinetic results on medium effects has verified the accuracy of the QM/MM approach in the full range of solvents from hydrocarbons to water to ionic liquids. Corresponding results from ab initio and density functional theory (DFT) methods with continuum-based treatments of solvation reveal deficiencies, particularly for protic solvents. Also summarized in this Account are three specific QM/MM applications to biomolecular systems: (1) a recent study that clarified the mechanism for the reaction of 2-pyrone derivatives catalyzed by macrophomate synthase as a tandem Michael-aldol sequence rather than a Diels-Alder reaction, (2) elucidation of the mechanism of action of fatty acid amide hydrolase (FAAH), an unusual Ser-Ser-Lys proteolytic enzyme, and (3) the construction of enzymes for Kemp elimination of 5-nitrobenzisoxazole that highlights the utility of QM/MM in the design of artificial enzymes.

Rare actinomycetes Nocardia caishijiensis and Pseudonocardia carboxydivorans as endophytes, their bioactivity and metabolites evaluation.

PubMed

Tanvir, Rabia; Sajid, Imran; Hasnain, Shahida; Kulik, Andreas; Grond, Stephanie

2016-04-01

Two strains identified as Nocardia caishijiensis (SORS 64b) and Pseudonocardia carboxydivorans (AGLS 2) were isolated as endophytes from Sonchus oleraceus and Ageratum conyzoides respectively. The analysis of their extracts revealed them to be strongly bioactive. The N. caishijiensis extract gave an LC50 of 570 μg/ml(-1) in the brine shrimp cytotoxicity assay and an EC50 of 0.552 μg/ml(-1) in the DPPH antioxidant assay. Antimicrobial activity was observed against Methicillin resistant Staphlococcus aureus (MRSA) and Escherichia coli ATCC 25922 (14 mm), Klebsiella pneumoniae ATCC 706003 (13 mm), S. aureus ATCC 25923 (11 mm) and Candida tropicalis (20 mm). For the extract of P. carboxydivorans the EC50 was 0.670 μg/ml(-1) and it was observed to be more bioactive against Bacillus subtilis DSM 10 ATCC 6051 (21 mm), C. tropicalis (20 mm), S. aureus ATCC 25923 (17 mm), MRSA (17 mm), E. coli K12 (W1130) (16 mm) and Chlorella vulgaris (10 mm). The genotoxicity testing revealed a 20 mm zone of inhibition against the polA mutant strain E. coli K-12 AB 3027 suggesting damage to the DNA and polA genes. The TLC and bioautography screening revealed a diversity of active bands of medium polar and nonpolar compounds. Metabolite analysis by HPLC-DAD via UV/vis spectral screening suggested the possibility of stenothricin and bagremycin A in the mycelium extract of N. caishijiensis respectively. In the broth and mycelium extract of P. carboxydivorans borrelidin was suggested along with α-pyrone. The HPLC-MS revealed bioactive long chained amide derivatives such as 7-Octadecenamide, 9, 12 octadecandienamide. This study reports the rare actinomycetes N. caishijiensis and P. carboxydivorans as endophytes and evaluates their bioactive metabolites. Copyright © 2016 Elsevier GmbH. All rights reserved.

Domain analysis of 3 Keto Acyl-CoA synthase for structural variations in Vitis vinifera and Oryza brachyantha using comparative modelling.

PubMed

Sagar, Mamta; Pandey, Neetesh; Qamar, Naseha; Singh, Brijendra; Shukla, Akanksha

2015-03-01

The long chain fatty acids incorporated into plant lipids are derived from the iterative addition of C2 units which is provided by malonyl-CoA to an acyl-CoA after interactions with 3-ketoacyl-CoA synthase (KCS), found in several plants. This study provides functional characterization of three 3 ketoacyl CoA synthase like proteins in Vitis vinifera (one) and Oryza brachyantha (two proteins). Sequence analysis reveals that protein of Oryza brachyantha shows 96% similarity to a hypothetical protein in Sorghum bicolor; total 11 homologs were predicted in Sorghum bicolor. Conserved domain prediction confirm the presence of FAE1/Type III polyketide synthase-like protein, Thiolase-like, subgroup; Thiolase-like and 3-Oxoacyl-ACP synthase III, C-terminal and chalcone synthase like domain but very long chain 3-keto acyl CoA domain is absent. All three proteins were found to have Chalcone and stilbene synthases C terminal domain which is similar to domain of thiolase and β keto acyl synthase. Its N terminal domain is absent in J3M9Z7 protein of Oryza brachyantha and F6HH63 protein of Vitis vinifera. Differences in N-terminal domain is responsible for distinguish activity. The J3MF16 protein of Oryza brachyantha contains N terminal domain and C terminal domain and characterized using annotation of these domains. Domains Gcs (streptomyces coelicolor) and Chalcone-stilbene synthases (KAS) in 2-pyrone synthase (Gerbera hybrid) and chalcone synthase 2 (Medicago sativa) were found to be present in three proteins. This similarity points toward anthocyanin biosynthetic process. Similarity to chalcone synthase 2 reveals its possible role in Naringenine and Chalcone synthase like activity. In 3 keto acyl CoA synthase of Oryza brachyantha. Active site residues C-240, H-407, N-447 are present in J3MF16 protein that are common in these three protein at different positions. Structural variations among dimer interface, product binding site, malonyl-CoA binding sites, were predicted in localized combination of conserved residues.

Carboxylate-assisted ruthenium-catalyzed alkyne annulations by C-H/Het-H bond functionalizations.

PubMed

Ackermann, Lutz

2014-02-18

To improve the atom- and step-economy of organic syntheses, researchers would like to capitalize upon the chemistry of otherwise inert carbon-hydrogen (C-H) bonds. During the past decade, remarkable progress in organometallic chemistry has set the stage for the development of increasingly viable metal catalysts for C-H bond activation reactions. Among these methods, oxidative C-H bond functionalizations are particularly attractive because they avoid the use of prefunctionalized starting materials. For example, oxidative annulations that involve sequential C-H and heteroatom-H bond cleavages allow for the modular assembly of regioselectively decorated heterocycles. These structures serve as key scaffolds for natural products, functional materials, crop protecting agents, and drugs. While other researchers have devised rhodium or palladium complexes for oxidative alkyne annulations, my laboratory has focused on the application of significantly less expensive, yet highly selective ruthenium complexes. This Account summarizes the evolution of versatile ruthenium(II) complexes for annulations of alkynes via C-H/N-H, C-H/O-H, or C-H/N-O bond cleavages. To achieve selective C-H bond functionalizations, we needed to understand the detailed mechanism of the crucial C-H bond metalation with ruthenium(II) complexes and particularly the importance of carboxylate assistance in this process. As a consequence, our recent efforts have resulted in widely applicable methods for the versatile preparation of differently decorated arenes and heteroarenes, providing access to among others isoquinolones, 2-pyridones, isoquinolines, indoles, pyrroles, or α-pyrones. Most of these reactions used Cu(OAc)2·H2O, which not only acted as the oxidant but also served as the essential source of acetate for the carboxylate-assisted ruthenation manifold. Notably, the ruthenium(II)-catalyzed oxidative annulations also occurred under an ambient atmosphere of air with cocatalytic amounts of Cu(OAc)2·H2O. Moreover, substrates displaying N-O bonds served as "internal oxidants" for the syntheses of isoquinolones and isoquinolines. Detailed experimental mechanistic studies have provided strong support for a catalytic cycle that relies on initial carboxylate-assisted C-H bond ruthenation, followed by coordinative insertion of the alkyne, reductive elimination, and reoxidation of the thus formed ruthenium(0) complex.

Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats.

PubMed

Surapaneni, Dinesh Kumar; Adapa, Sree Rama Shiva Shanker; Preeti, Kumari; Teja, Gangineni Ravi; Veeraragavan, Muruganandam; Krishnamurthy, Sairam

2012-08-30

Shilajit has been used as a rejuvenator for ages in Indian ancient traditional medicine and has been validated for a number of pharmacological activities. The effect of processed shilajit which was standardized to dibenzo-α-pyrones (DBPs;0.43% w/w), DBP-chromoproteins (DCPs; 20.45% w/w) and fulvic acids (56.75% w/w) was evaluated in a rat model of chronic fatigue syndrome (CFS). The mitochondrial bioenergetics and the activity of hypothalamus-pituitary-adrenal (HPA) axis were evaluated for the plausible mechanism of action of shilajit. CFS was induced by forcing the rats to swim for 15mins for 21 consecutive days. The rats were treated with shilajit (25, 50 and 100mg/kg) for 21 days before exposure to stress procedure. The behavioral consequence of CFS was measured in terms of immobility and the climbing period. The post-CFS anxiety level was assessed by elevated plus maze (EPM) test. Plasma corticosterone and adrenal gland weight were estimated as indices of HPA axis activity. Analysis of mitochondrial complex chain enzymes (Complex I, II, IV and V) and mitochondrial membrane potential (MMP) in prefrontal cortex (PFC) were performed to evaluate the mitochondrial bioenergetics and integrity respectively. Shilajit reversed the CFS-induced increase in immobility period and decrease in climbing behavior as well as attenuated anxiety in the EPM test. Shilajit reversed CFS-induced decrease in plasma corticosterone level and loss of adrenal gland weight indicating modulation of HPA axis. Shilajit prevented CFS-induced mitochondrial dysfunction by stabilizing the complex enzyme activities and the loss of MMP. Shilajit reversed CFS-induced mitochondrial oxidative stress in terms of NO concentration and, LPO, SOD and catalase activities. The results indicate that shilajit mitigates the effects of CFS in this model possibly through the modulation of HPA axis and preservation of mitochondrial function and integrity. The reversal of CFS-induced behavioral symptoms and mitochondrial bioenergetics by shilajit indicates mitochondria as a potential target for treatment of CFS. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Engineering cofactor and transport mechanisms in Saccharomyces cerevisiae for enhanced acetyl-CoA and polyketide biosynthesis.

PubMed

Cardenas, Javier; Da Silva, Nancy A

2016-07-01

Synthesis of polyketides at high titer and yield is important for producing pharmaceuticals and biorenewable chemical precursors. In this work, we engineered cofactor and transport pathways in Saccharomyces cerevisiae to increase acetyl-CoA, an important polyketide building block. The highly regulated yeast pyruvate dehydrogenase bypass pathway was supplemented by overexpressing a modified Escherichia coli pyruvate dehydrogenase complex (PDHm) that accepts NADP(+) for acetyl-CoA production. After 24h of cultivation, a 3.7-fold increase in NADPH/NADP(+) ratio was observed relative to the base strain, and a 2.2-fold increase relative to introduction of the native E. coli PDH. Both E. coli pathways increased acetyl-CoA levels approximately 2-fold relative to the yeast base strain. Combining PDHm with a ZWF1 deletion to block the major yeast NADPH biosynthesis pathway resulted in a 12-fold NADPH boost and a 2.2-fold increase in acetyl-CoA. At 48h, only this coupled approach showed increased acetyl-CoA levels, 3.0-fold higher than that of the base strain. The impact on polyketide synthesis was evaluated in a S. cerevisiae strain expressing the Gerbera hybrida 2-pyrone synthase (2-PS) for the production of the polyketide triacetic acid lactone (TAL). Titers of TAL relative to the base strain improved only 30% with the native E. coli PDH, but 3.0-fold with PDHm and 4.4-fold with PDHm in the Δzwf1 strain. Carbon was further routed toward TAL production by reducing mitochondrial transport of pyruvate and acetyl-CoA; deletions in genes POR2, MPC2, PDA1, or YAT2 each increased titer 2-3-fold over the base strain (up to 0.8g/L), and in combination to 1.4g/L. Combining the two approaches (NADPH-generating acetyl-CoA pathway plus reduced metabolite flux into the mitochondria) resulted in a final TAL titer of 1.6g/L, a 6.4-fold increase over the non-engineered yeast strain, and 35% of theoretical yield (0.16g/g glucose), the highest reported to date. These biological driving forces present new avenues for improving high-yield production of acetyl-CoA derived compounds. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Crystal structure of bis­{μ2-2,2′-[(4,10-dimethyl-1,4,7,10-tetra­aza­cyclo­dodecane-1,7-di­yl)bis(meth­yl­ene)]bis­(4-oxo-4H-pyran-3-olato)}dicobalt­calcium bis­(perchlorate) 1.36-hydrate

PubMed Central

Rossi, Patrizia; Paoli, Paola; Giorgi, Luca; Formica, Mauro; Fusi, Vieri

2017-01-01

The title compound, [CaCo2(C22H30N4O6)2](ClO4)2·1.36H2O or {Ca[Co(H–2 L1)]2}·2ClO4·1.36H2O {where L1 is 4,10-bis­[(3-hy­droxy-4-pyron-2-yl)meth­yl]-1,7-dimethyl-1,4,7,10-tetra­aza­cyclo­dodecane}, is a trinuclear complex whose asymmetric unit comprises a quarter of the {Ca[Co(H–2 L1)]2}2+ trinuclear complex, half of a perchlorate ion and 0.34-water mol­ecules. In the neutral [Co(H–2 L1)] moiety, the cobalt ion is hexa­coordinated in a trigonal–prismatic fashion by the surrounding N4O2 donor set. A Ca2+ cation holds together two neutral [Co(H–2 L1)] moieties and is octa­coordinated in a distorted trigonal–dodeca­hedral fashion by the surrounding O atoms belonging to the deprotonated oxide and carbonyl groups of two [Co(H–2 L1)] units. The coordination of the CoII cation preorganizes L1 and an electron-rich area forms, which is able to host hard metal ions. The comparison between the present structure and the previously published ones suggests a high versatility of this ligand; indeed, hard metal ions with different nature and dimensions lead to complexes having different stoichiometry (mono- and dinuclear monomers and trinuclear dimers) or even a polymeric structure. The heterotrinuclear CoII–CaII–CoII complexes are connected in three dimensions via weak C—H⋯O hydrogen bonds, which are also responsible for the inter­actions with the perchlorate anions and the lattice water mol­ecules. The perchlorate anion is disordered about a twofold rotation axis and was refined giving the two positions a fixed occupancy factor of 0.5. The crystal studied was refined as a two-component inversion twin [BASF parameter = 0.14 (4)]. PMID:29250424

Microbial biotransformation of bioactive flavonoids.

PubMed

Cao, Hui; Chen, Xiaoqing; Jassbi, Amir Reza; Xiao, Jianbo

2015-01-01

The bioactive flavonoids are considered as the most important phytochemicals in food, which exert a wide range of biological benefits for human being. Microbial biotransformation strategies for production of flavonoids have attracted considerable interest because they allow yielding novel flavonoids, which do not exist in nature. In this review, we summarize the existing knowledge on the production and biotransformation of flavonoids by various microbes. The main reactions during microbial biotransformation are hydroxylation, dehydroxylation, O-methylation, O-demethylation, glycosylation, deglycosylation, dehydrogenation, hydrogenation, C ring cleavage of the benzo-γ-pyrone system, cyclization, and carbonyl reduction. Cunninghamella, Penicillium, and Aspergillus strains are very popular to biotransform flavonoids and they can perform almost all the reactions with excellent yields. Aspergillus niger is one of the most applied microorganisms in the flavonoids' biotransformation; for example, A. niger can transfer flavanone to flavan-4-ol, 2'-hydroxydihydrochalcone, flavone, 3-hydroxyflavone, 6-hydroxyflavanone, and 4'-hydroxyflavanone. The hydroxylation of flavones by microbes usually happens on the ortho position of hydroxyl group on the A ring and C-4' position of the B ring and microbes commonly hydroxylate flavonols at the C-8 position. The microorganisms tend to hydroxylate flavanones at the C-5, 6, and 4' positions; however, for prenylated flavanones, dihydroxylation often takes place on the C4α=C5α double bond on the prenyl group (the side chain of A ring). Isoflavones are usually hydroxylated at the C-3' position of the B ring by microorganisms. The microbes convert flavonoids to their 7-O-glycosides and 3-O-glycosides (when flavonoids have a hydroxyl moiety at the C-3 position). The demethylation of multimethoxyl flavonoids by microbes tends to happen at the C-3' and C-4' positions of the B ring. Multimethoxyl flavanones and isoflavone are demethylated at the C-7 and C-4' positions. The O-methylation of flavonols happens at the C-3' and C-4' and microorganisms O-methylate flavones at the C-6 position and the O-methylation of flavanones, usually took place on the hydroxyl groups of the A ring. The prenyl flavanones were cyclized at the prenyl side chain to form a new five-member ring attached to the A ring. Chalcones were regioselectively cyclized to flavanones. Hydrogenation of flavonoids was only reported on transformation of chalcones to dihydrochalcones. The dehydrogenation of flavanoids to flavonoids was not comprehensively studied. Copyright © 2014 Elsevier Inc. All rights reserved.

Involvement of the Transcriptional Coactivator ThMBF1 in the Biocontrol Activity of Trichoderma harzianum.

PubMed

Rubio, M Belén; Pardal, Alonso J; Cardoza, Rosa E; Gutiérrez, Santiago; Monte, Enrique; Hermosa, Rosa

2017-01-01

Trichoderma harzianum is a filamentous fungus well adapted to different ecological niches. Owing to its ability to antagonize a wide range of plant pathogens, it is used as a biological control agent in agriculture. Selected strains of T. harzianum are also able to increase the tolerance of plants to biotic and abiotic stresses. However, little is known about the regulatory elements of the T. harzianum transcriptional machinery and their role in the biocontrol by this species. We had previously reported the involvement of the transcription factor THCTF1 in the T. harzianum production of the secondary metabolite 6-pentyl-pyrone, an important volatile compound related to interspecies cross-talk. Here, we performed a subtractive hybridization to explore the genes regulated by THCTF1, allowing us to identify a multiprotein bridging factor 1 ( mbf1 ) homolog. The gene from T. harzianum T34 was isolated and characterized, and the generated Thmbf1 overexpressing transformants were used to investigate the role of this gene in the biocontrol abilities of the fungus against two plant pathogens. The transformants showed a reduced antifungal activity against Fusarium oxysporum f. sp. lycopersici race 2 (FO) and Botrytis cinerea (BC) in confrontation assays on discontinuous medium, indicating that the Thmbf1 gene could affect T. harzianum production of volatile organic compounds (VOC) with antifungal activity. Moreover, cellophane and dialysis membrane assays indicated that Thmbf1 overexpression affected the production of low molecular weight secreted compounds with antifungal activity against FO. Intriguingly, no correlation in the expression profiles, either in rich or minimal medium, was observed between Thmbf1 and the master regulator gene cross-pathway control ( cpc1 ). Greenhouse assays allowed us to evaluate the biocontrol potential of T. harzianum strains against BC and FO on susceptible tomato plants. The wild type strain T34 significantly reduced the necrotic leaf lesions caused by BC while plants treated with the Thmbf1 -overexpressing transformants exhibited an increased susceptibility to this pathogen. The percentages of Fusarium wilt disease incidence and values of aboveground dry weight showed that T34 did not have biocontrol activity against FO, at least in the 'Moneymaker' tomato variety, and that Thmbf1 overexpression increased the incidence of this disease. Our results show that the Thmbf1 overexpression in T34 negatively affects its biocontrol mechanisms.

Involvement of the Transcriptional Coactivator ThMBF1 in the Biocontrol Activity of Trichoderma harzianum

PubMed Central

Rubio, M. Belén; Pardal, Alonso J.; Cardoza, Rosa E.; Gutiérrez, Santiago; Monte, Enrique; Hermosa, Rosa

2017-01-01

Trichoderma harzianum is a filamentous fungus well adapted to different ecological niches. Owing to its ability to antagonize a wide range of plant pathogens, it is used as a biological control agent in agriculture. Selected strains of T. harzianum are also able to increase the tolerance of plants to biotic and abiotic stresses. However, little is known about the regulatory elements of the T. harzianum transcriptional machinery and their role in the biocontrol by this species. We had previously reported the involvement of the transcription factor THCTF1 in the T. harzianum production of the secondary metabolite 6-pentyl-pyrone, an important volatile compound related to interspecies cross-talk. Here, we performed a subtractive hybridization to explore the genes regulated by THCTF1, allowing us to identify a multiprotein bridging factor 1 (mbf1) homolog. The gene from T. harzianum T34 was isolated and characterized, and the generated Thmbf1 overexpressing transformants were used to investigate the role of this gene in the biocontrol abilities of the fungus against two plant pathogens. The transformants showed a reduced antifungal activity against Fusarium oxysporum f. sp. lycopersici race 2 (FO) and Botrytis cinerea (BC) in confrontation assays on discontinuous medium, indicating that the Thmbf1 gene could affect T. harzianum production of volatile organic compounds (VOC) with antifungal activity. Moreover, cellophane and dialysis membrane assays indicated that Thmbf1 overexpression affected the production of low molecular weight secreted compounds with antifungal activity against FO. Intriguingly, no correlation in the expression profiles, either in rich or minimal medium, was observed between Thmbf1 and the master regulator gene cross-pathway control (cpc1). Greenhouse assays allowed us to evaluate the biocontrol potential of T. harzianum strains against BC and FO on susceptible tomato plants. The wild type strain T34 significantly reduced the necrotic leaf lesions caused by BC while plants treated with the Thmbf1-overexpressing transformants exhibited an increased susceptibility to this pathogen. The percentages of Fusarium wilt disease incidence and values of aboveground dry weight showed that T34 did not have biocontrol activity against FO, at least in the ‘Moneymaker’ tomato variety, and that Thmbf1 overexpression increased the incidence of this disease. Our results show that the Thmbf1 overexpression in T34 negatively affects its biocontrol mechanisms. PMID:29201024

Design, synthesis, and evaluation of bioactive molecules; Quantification of tricyclic pyrones from pharmacokinetic studies; Nanodelivery of siRNA; and Synthesis of viral protease inhibitors

NASA Astrophysics Data System (ADS)

Weerasekara, Sahani Manjitha

Four research projects were carried out and they are described in this dissertation. Glycogen synthase kinase-3 beta (GSK3?) plays a pivotal and central role in the pathogenesis of Alzheimer's disease (AD) and protein kinase C (PKC) controls the function of other proteins via phosphorylation and involves in tumor promotion. In pursuit of identifying novel GSK3beta and/or PKC inhibitors, substituted quinoline molecules were designed and synthesized based on the structure-activity-relationship studies. Synthesized molecules were evaluated for their neural protective activities and selected molecules were further tested for inhibitory activities on GSK3beta and PKC enzymes. Among these compounds, compound 2 was found to have better GSK3beta enzyme inhibitory and MC65 cell protection activities at low nanomolar concentrations and poor PKC inhibitory activity whereas compound 3 shows better PKC inhibitory activity. This demonstrates the potential for uses of quinoline scaffold in designing novel compounds for AD and cancer. Pharmacokinetics and distribution profiles of two anti-Alzheimer molecules, CP2 and TP70, discovered in our laboratory were assessed using HPLC/MS. Plasma samples of mice and rats fed with TP70 via different routes over various times were analyzed to quantify the amounts of TP70 in plasma of both species. Distribution profiles of TP70 in various tissues of mice were studied and results show that TP70 penetrated the blood brain barrier and accumulated in the brain tissue in significant amounts. Similarly, the amount of CP2 in plasma of mice was analyzed. The HPLC analysis revealed that both compounds have good PK profiles and bioavailability, which would make them suitable candidates for further in vivo efficacy studies. Nanodelivery of specific dsRNA for suppressing the western corn rootworm (WCR, Diabrotica virgifera virgifera) genes was studied using modified chitosan or modified polyvinylpyrrolidinone (PVP) as nanocarriers. Computational simulation studies of dsRNA with these polymers revealed that nanoparticles can be formed between dsRNA and modified chitosan and PVP polymers. Nanocarriers of hydroxylated PVP (HO-PVP) and chitosan conjugated with polyethylene glycol (PEG) were synthesized, and analyzed using IR spectroscopy. Particle sizes and morphology were evaluated using AFM and encapsulation was studied using UV spectroscopy. However, the formation of stable nanoparticles with dsRNA could not be achieved with either of the polymers, and further efforts are ongoing to discover a better nanocarrier for nanodelivery of siRNA by using chitosan-galactose nanocarrier. In our efforts to discover a novel class of tripeptidyl anti-norovirus compounds that can strongly inhibit NV3CLpro, a set of tripeptidyl molecules were synthesized by modifying the P1 - P3 of the substrate peptide including a warhead. It was found that the replacement of P1 glutamine surrogate with triazole functionality does not improve the inhibitory activities of the compounds. In addition, the synthesis of a known dipeptidyl compound (GC376) was carried out for evaluating its efficacy on feline infectious peritonitis (FIP) in cats.