Niduenes A-F(1-6),six novel sesterterpenoids with unprecedented 5/5/5/5/6 pentacyclic ring skeleton were isolated from endophytic fungus Aspergillus nidulans.Compounds 1 and 2 represent the first examples of aromatic ...Niduenes A-F(1-6),six novel sesterterpenoids with unprecedented 5/5/5/5/6 pentacyclic ring skeleton were isolated from endophytic fungus Aspergillus nidulans.Compounds 1 and 2 represent the first examples of aromatic pentacyclic sesterterpenoids.Their structures and configurations were elucidated by spectroscopic data and single-crystal X-ray diffraction analyses.Compound 4 demonstrated potent resensitization of SW620/AD300 cells to paclitaxel(PTX).Rhodamine 123 accumulation assay and docking analysis further support that 4 inhibitory the efflux function of P-glycoprotein(P-gp).展开更多
Three novel sesterterpenoids glasesterterpenoids A-C(1-3),featuring an unprecedented 7-cyclohexyldecahydronaphthalene carbon skeleton,were isolated from the root of Lindera glauca(L.glauca).Their structures were eluci...Three novel sesterterpenoids glasesterterpenoids A-C(1-3),featuring an unprecedented 7-cyclohexyldecahydronaphthalene carbon skeleton,were isolated from the root of Lindera glauca(L.glauca).Their structures were elucidated by quantum chemical calculations and spectroscopic methods.The biogenetic pathway for 1-3 is proposed.In the bioassay,glasesterterpenoid C exhibited DNA topoisomerase 1(Top1)inhibitory activity compared with the positive control,camptothecin.These findings represent the first examples of sesterterpenoids with a 7-cyclohexyldecahydronaphthalene carbon skeleton from the root of L.glauca.展开更多
This review covers the isolation,structural determination,plausible biosynthetic pathways,and biological activities of 166 natural terpenoids including 57 sesquiterpenoids,65 diterpenoids,15 sesterterpenoids,and 29 tr...This review covers the isolation,structural determination,plausible biosynthetic pathways,and biological activities of 166 natural terpenoids including 57 sesquiterpenoids,65 diterpenoids,15 sesterterpenoids,and 29 triterpenoids from January 2017 to December2022.展开更多
Two chimeric sesterterpene synthases(Aa TPS1 and Aa TPS2)were functionally characterized from Alternaria alternata MB-30 isolated from the leaves of a sesterterpenoid-producing Lamiaceae plant Leucosceptrum canum.Aa T...Two chimeric sesterterpene synthases(Aa TPS1 and Aa TPS2)were functionally characterized from Alternaria alternata MB-30 isolated from the leaves of a sesterterpenoid-producing Lamiaceae plant Leucosceptrum canum.Aa TPS1 generated a 5/8/6/5 tetracyclic sesteraltererol(1)and its absolute stereochemistry was determined by X-ray crystallographic analysis of its derivative 10,11-epoxysesteraltererol(2),which enabled revision of the absolute configuration of C7 of sesterfisherol produced by Nf SS and PTTS014 characterized previously and its derivative 10,11-epoxysesterfisherol.Aa TPS2 produced a 5/15 bicyclic preterpestacin I(3).Site-directed mutagenesis suggested that F192 in Aa TPS1 was likely involved in controlling of the hydroxylation of C12,and eight amino acids were important for the enzyme activity of Aa TPS1 and Aa TPS2.The engineered Escherichia coli and Saccharomyces cerevisiae strains were constructed for the productions of compounds 1 and 3,and the highest titer of compound 1 reached 62.3 mg/L in shake-flask culture.Both compounds 1 and 2 showed anti-adipogenic activity.展开更多
Obesity that is highly associated with numerous metabolic diseases has become a global health issue nowdays.Plant sesterterpenoids are an important group of natural products with great potential;thus,their bioactiviti...Obesity that is highly associated with numerous metabolic diseases has become a global health issue nowdays.Plant sesterterpenoids are an important group of natural products with great potential;thus,their bioactivities deserve extensive exploration.RNA-seq analysis indicated that leucosceptroid B,a sesterterpenoid previously discovered from the glandular trichomes of Leucosceptrum canum,significantly regulated the expression of 10 genes involved in lipid metabolism in Caenorhabditis elegans.Furthermore,leucosceptroid B was found to reduce fat storage,and downregulate the expression of two stearoyl-CoA desaturase(SCD)genes fat-6 and fat-7,and a fatty acid elongase gene elo-2 in wild-type C.elegans.In addition,leucosceptroid B significantly decreased fat accumulation in both fat-6 and fat-7 mutant worms but did not affect the fat storage of fat-6;fat-7 double mutant.These findings indicated that leucosceptroid B reduced fat storage depending on the downregulated expression of fat-6,fat-7 and elo-2 and thereby inhibiting the biosynthesis of the corresponding unsaturated fatty acid.These findings provide new insights into the development and utilization of plant sesterterpenoids as potential antilipemic agents.展开更多
A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC 16872.Heterologous production of 1 and 2 was achieved in Aspergillus...A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC 16872.Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB.Intriguingly,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic window.Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.展开更多
基金financially supported by the National Key Research and Development Program of China(No.2021YFA0910500)the National Natural Science Foundation of China(Nos.U22A20380,82104028,82173706 and 82373755)+2 种基金Innovative Research Groups of the National Natural Science Foundation of China(No.81721005)the Science and Technology Major Project of Hubei Province(No.2021ACA012)the Fundamental Research Funds for the Central Universities,HUST(No.2021JYCXJJ058)。
文摘Niduenes A-F(1-6),six novel sesterterpenoids with unprecedented 5/5/5/5/6 pentacyclic ring skeleton were isolated from endophytic fungus Aspergillus nidulans.Compounds 1 and 2 represent the first examples of aromatic pentacyclic sesterterpenoids.Their structures and configurations were elucidated by spectroscopic data and single-crystal X-ray diffraction analyses.Compound 4 demonstrated potent resensitization of SW620/AD300 cells to paclitaxel(PTX).Rhodamine 123 accumulation assay and docking analysis further support that 4 inhibitory the efflux function of P-glycoprotein(P-gp).
基金supported by the National Natural Science Foundation of China(No.82104524)the Basic and Applied Research Program of Guangzhou City(No.2024A04J9954)。
文摘Three novel sesterterpenoids glasesterterpenoids A-C(1-3),featuring an unprecedented 7-cyclohexyldecahydronaphthalene carbon skeleton,were isolated from the root of Lindera glauca(L.glauca).Their structures were elucidated by quantum chemical calculations and spectroscopic methods.The biogenetic pathway for 1-3 is proposed.In the bioassay,glasesterterpenoid C exhibited DNA topoisomerase 1(Top1)inhibitory activity compared with the positive control,camptothecin.These findings represent the first examples of sesterterpenoids with a 7-cyclohexyldecahydronaphthalene carbon skeleton from the root of L.glauca.
文摘This review covers the isolation,structural determination,plausible biosynthetic pathways,and biological activities of 166 natural terpenoids including 57 sesquiterpenoids,65 diterpenoids,15 sesterterpenoids,and 29 triterpenoids from January 2017 to December2022.
基金supported financially by the National Natural Science Foundation of China(Nos.21937006 and 22107103)the Yunnan Key Research and Development Program(No.2019ZF011–2)the“Western Light”Program of the CAS(to Y.Liu)。
文摘Two chimeric sesterterpene synthases(Aa TPS1 and Aa TPS2)were functionally characterized from Alternaria alternata MB-30 isolated from the leaves of a sesterterpenoid-producing Lamiaceae plant Leucosceptrum canum.Aa TPS1 generated a 5/8/6/5 tetracyclic sesteraltererol(1)and its absolute stereochemistry was determined by X-ray crystallographic analysis of its derivative 10,11-epoxysesteraltererol(2),which enabled revision of the absolute configuration of C7 of sesterfisherol produced by Nf SS and PTTS014 characterized previously and its derivative 10,11-epoxysesterfisherol.Aa TPS2 produced a 5/15 bicyclic preterpestacin I(3).Site-directed mutagenesis suggested that F192 in Aa TPS1 was likely involved in controlling of the hydroxylation of C12,and eight amino acids were important for the enzyme activity of Aa TPS1 and Aa TPS2.The engineered Escherichia coli and Saccharomyces cerevisiae strains were constructed for the productions of compounds 1 and 3,and the highest titer of compound 1 reached 62.3 mg/L in shake-flask culture.Both compounds 1 and 2 showed anti-adipogenic activity.
基金supported by the National Science Fund for Distinguished Young Scholars(No.31525005)National Natural Science Foundation of China(Nos.21937006,31770390 and 31800298)+3 种基金Yunnan Key Research and Development Program(No.2019ZF011-2)Yunnan Innovative Research Team for Discovery and Biosynthesis of Bioactive Natural Products(No.2018HC012)Science Foundation of Yunnan(No.2018FA017)Youth Innovation Promotion Association and “Western Light” Program of CAS(awarded to LIU Yan)
文摘Obesity that is highly associated with numerous metabolic diseases has become a global health issue nowdays.Plant sesterterpenoids are an important group of natural products with great potential;thus,their bioactivities deserve extensive exploration.RNA-seq analysis indicated that leucosceptroid B,a sesterterpenoid previously discovered from the glandular trichomes of Leucosceptrum canum,significantly regulated the expression of 10 genes involved in lipid metabolism in Caenorhabditis elegans.Furthermore,leucosceptroid B was found to reduce fat storage,and downregulate the expression of two stearoyl-CoA desaturase(SCD)genes fat-6 and fat-7,and a fatty acid elongase gene elo-2 in wild-type C.elegans.In addition,leucosceptroid B significantly decreased fat accumulation in both fat-6 and fat-7 mutant worms but did not affect the fat storage of fat-6;fat-7 double mutant.These findings indicated that leucosceptroid B reduced fat storage depending on the downregulated expression of fat-6,fat-7 and elo-2 and thereby inhibiting the biosynthesis of the corresponding unsaturated fatty acid.These findings provide new insights into the development and utilization of plant sesterterpenoids as potential antilipemic agents.
基金This work was performed for the iGEM 2021 Competition,and the financial support received from the Department of Chemistry,City University of Hong Kong,is greatly appreciated.We also thank Prof.Katsuya Gomi(Tohoku University)and Profs.Katsuhiko Kitamoto and Jun-ichi Maruyama(The University of Tokyo)for providing the expression vectors and the fungal strain.We are grateful to Dr.Man-Kit Tse(City University of Hong Kong)and Dr.Shek-Man Yiu(City University of Hong Kong)for their assistance with NMR spectra acquisition and X-ray diffraction data collection and analysis,respectively.This work was supported in part by an Early Career Scheme grant from the Research Grants Council(RGC)of Hong Kong(Project No.21300219(Y.M))M.V.B acknowledges support from the City University of Hong Kong(Project No.9610518).
文摘A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC 16872.Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB.Intriguingly,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic window.Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.
