目的对单菌多次级代谢产物(One strain many compounds,OSMAC)策略在微生物次级代谢产物研究中的应用进展进行综述。方法查阅近年来的相关文献,对微生物次级代谢产物研究中所应用的OSMAC策略进行分类和归纳总结。结果近年来所应用的OSMA...目的对单菌多次级代谢产物(One strain many compounds,OSMAC)策略在微生物次级代谢产物研究中的应用进展进行综述。方法查阅近年来的相关文献,对微生物次级代谢产物研究中所应用的OSMAC策略进行分类和归纳总结。结果近年来所应用的OSMAC策略主要包括改变培养基、改变培养条件或培养状态、混合培养、化学表观遗传修饰、添加酶抑制剂或其他物质等。结论OSMAC策略在激活微生物沉默基因、增加次级代谢产物多样性方面发挥了重要作用,随着现代科学技术的发展,OSMAC策略与新技术结合必然会成为发现新药和先导化合物的一条重要途径。展开更多
Four extracts of the marine-derived fungus Penicillium velutinum J.F.H.Beyma were obtained via metal ions stress conditions based on the OSMAC(One Strain Many Compounds)strategy.Using a combination of modern approache...Four extracts of the marine-derived fungus Penicillium velutinum J.F.H.Beyma were obtained via metal ions stress conditions based on the OSMAC(One Strain Many Compounds)strategy.Using a combination of modern approaches such as LC/UV,LC/MS and bioactivity data analysis,as well as in silico calculations,influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed.From the ethyl acetate extract of the P.velutinum were isolated two new piperazine derivatives helvamides B(1)and C(2)together with known saroclazin A(3)(4S,5R,7S)-4,11-dihydroxy-guaia-1(2),9(10)-dien(4).Their structures were established based on spectroscopic methods.The absolute configuration of helvamide B(1)as 2R,5R was determined by a combination of the X-ray analysis and by time-dependent density functional theory(TD-DFT)calculations of electronic circular dichroism(ECD)spectra.The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed.展开更多
The growing number of sequenced microbial genomes has revealed a remarkably large number of secondary metabolite biosynthetic clusters for which the compounds are still unknown.The aim of the present work was to apply...The growing number of sequenced microbial genomes has revealed a remarkably large number of secondary metabolite biosynthetic clusters for which the compounds are still unknown.The aim of the present work was to apply a strategy to detect newly induced natural products by cultivating microorganisms in different fermentation conditions.The metabolomic analysis of 4160 fractions generated from 13 actinomycetes under 32 different culture conditions was carried out by 1H NMR spectroscopy and multivariate analysis.The principal component analysis(PCA)of the 1H NMR spectra showed a clear discrimination between those samples within PC1 and PC2.The fractions with induced metabolites that are only produced under specific growth conditions was identified by PCA analysis.This method allows an efficient differentiation within a large dataset with only one fractionation step.This work demonstrates the potential of NMR spectroscopy in combination with metabolomic data analysis for the screening of large sets of fractions.展开更多
Nine novel compounds,comprising seven tetrahydroanthraquinones(auxarthrolones A−G,1−7),aγ-butenolide glycoside(malfilamentoside E,26),and aγ-butenolide(auxarthrolide A,27),together with eighteen known compounds(8−25...Nine novel compounds,comprising seven tetrahydroanthraquinones(auxarthrolones A−G,1−7),aγ-butenolide glycoside(malfilamentoside E,26),and aγ-butenolide(auxarthrolide A,27),together with eighteen known compounds(8−25)were isolated from rice-based solid culture of Auxarthron umbrinum(A.umbrinum)DSM3193 using the one strain many compounds(OSMAC)approach.The structural elucidation of these compounds was accomplished through nuclear magnetic resonance(NMR),mass spectrometry(MS),and NMR calculation combined with DP4+analysis or MAEΔΔδparameter,while the absolute configurations of new compounds were established through single-crystal X-ray diffraction,electronic circular dichroism(ECD)spectroscopic data analysis and/or chemical derivatization.Austrocortilutein(10)and auxarthrol H(14)demonstrated moderate cytotoxicity against U87 and U251[half maximal inhibitory concentration(IC_(50))3.5−12.1μmol·L^(−1)].Additionally,auxarthrolone A(1),auxarthrol H(14),eupolyphagin B(15),and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone(17)exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid,thus demonstrating fibroblast proliferation-promoting activity.展开更多
文摘目的对单菌多次级代谢产物(One strain many compounds,OSMAC)策略在微生物次级代谢产物研究中的应用进展进行综述。方法查阅近年来的相关文献,对微生物次级代谢产物研究中所应用的OSMAC策略进行分类和归纳总结。结果近年来所应用的OSMAC策略主要包括改变培养基、改变培养条件或培养状态、混合培养、化学表观遗传修饰、添加酶抑制剂或其他物质等。结论OSMAC策略在激活微生物沉默基因、增加次级代谢产物多样性方面发挥了重要作用,随着现代科学技术的发展,OSMAC策略与新技术结合必然会成为发现新药和先导化合物的一条重要途径。
基金funded by Russian Science Foundation,grant number№22-73-00190,https://rscf.ru/en/project/22-73-00190/.
文摘Four extracts of the marine-derived fungus Penicillium velutinum J.F.H.Beyma were obtained via metal ions stress conditions based on the OSMAC(One Strain Many Compounds)strategy.Using a combination of modern approaches such as LC/UV,LC/MS and bioactivity data analysis,as well as in silico calculations,influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed.From the ethyl acetate extract of the P.velutinum were isolated two new piperazine derivatives helvamides B(1)and C(2)together with known saroclazin A(3)(4S,5R,7S)-4,11-dihydroxy-guaia-1(2),9(10)-dien(4).Their structures were established based on spectroscopic methods.The absolute configuration of helvamide B(1)as 2R,5R was determined by a combination of the X-ray analysis and by time-dependent density functional theory(TD-DFT)calculations of electronic circular dichroism(ECD)spectra.The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed.
基金This research was supported by an Australian Research Council(ARC)Linkage Project DP160101429,ARC project LP120100485the Bill&Melinda Gates Foundation Grand Challenges Explorations Grant Phase Ⅱ OPP1035218 GCE.M.Liu thanks Griffith University for the Publication Assistance Scholarship.
文摘The growing number of sequenced microbial genomes has revealed a remarkably large number of secondary metabolite biosynthetic clusters for which the compounds are still unknown.The aim of the present work was to apply a strategy to detect newly induced natural products by cultivating microorganisms in different fermentation conditions.The metabolomic analysis of 4160 fractions generated from 13 actinomycetes under 32 different culture conditions was carried out by 1H NMR spectroscopy and multivariate analysis.The principal component analysis(PCA)of the 1H NMR spectra showed a clear discrimination between those samples within PC1 and PC2.The fractions with induced metabolites that are only produced under specific growth conditions was identified by PCA analysis.This method allows an efficient differentiation within a large dataset with only one fractionation step.This work demonstrates the potential of NMR spectroscopy in combination with metabolomic data analysis for the screening of large sets of fractions.
基金supported by the National Key Research and Development Program of China(No.2018YFA0901900)the National Science Fund for Distinguished Young Scholars(No.82225042).
文摘Nine novel compounds,comprising seven tetrahydroanthraquinones(auxarthrolones A−G,1−7),aγ-butenolide glycoside(malfilamentoside E,26),and aγ-butenolide(auxarthrolide A,27),together with eighteen known compounds(8−25)were isolated from rice-based solid culture of Auxarthron umbrinum(A.umbrinum)DSM3193 using the one strain many compounds(OSMAC)approach.The structural elucidation of these compounds was accomplished through nuclear magnetic resonance(NMR),mass spectrometry(MS),and NMR calculation combined with DP4+analysis or MAEΔΔδparameter,while the absolute configurations of new compounds were established through single-crystal X-ray diffraction,electronic circular dichroism(ECD)spectroscopic data analysis and/or chemical derivatization.Austrocortilutein(10)and auxarthrol H(14)demonstrated moderate cytotoxicity against U87 and U251[half maximal inhibitory concentration(IC_(50))3.5−12.1μmol·L^(−1)].Additionally,auxarthrolone A(1),auxarthrol H(14),eupolyphagin B(15),and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone(17)exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid,thus demonstrating fibroblast proliferation-promoting activity.
