(±)-Talapyrones A−F(1−6),six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems,were isolated from the fungus Talaromyces adpressus.Their structures were determined by spectr...(±)-Talapyrones A−F(1−6),six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems,were isolated from the fungus Talaromyces adpressus.Their structures were determined by spectroscopic analysis and HR-ESI-MS data,and their absolute configurations were elucidated using a modified Mosher’s method and electronic circular dichroism(ECD)calculations.(±)-Talapyrones A−F(1−6)possess a 6/6/6 tricyclic skeleton,presumably formed through a Michael addition reaction between one molecule ofα-pyrone derivative and one molecule of C8 poly-β-keto chain.In addition,compounds 2/3 and 4/5 are two pairs of C-18 epimers,respectively.Putative biosynthetic pathways of 1−6 were discussed.展开更多
Three novel,highly oxygenated polyketides,multioketides A-C(1-3),and three previously described multioxidized aromatic polyketides(4-6),were isolated from an endophytic Penicillium sp.YUD17006 associated with Gastrodi...Three novel,highly oxygenated polyketides,multioketides A-C(1-3),and three previously described multioxidized aromatic polyketides(4-6),were isolated from an endophytic Penicillium sp.YUD17006 associated with Gastrodia elata.Their chem-ical structures were elucidated using extensive spectroscopic data,electronic circular dichroism calculations,and single X-ray diffrac-tion analysis.All metabolites were characterized by a typical α,β-unsaturated ketone fragment and exhibited a high degree of oxidation.Multioketides A and B were identified as a pair of epimers featuring a rare dihydroisobenzofuranone core.Multioketide C possessed a novel 5/6/6/6 heterotetracyclic chemical architecture with unusual 1,4-dioxin functionalities.Plausible biosynthetic pathways for 1-6 were proposed.Additionally,compound 3 demonstrated weak inhibitory activities against both acetylcholinesterase and protein tyr-osine phosphatase 1B.展开更多
Polyketide synthases(PKSs)are megasynthases with multiple autonomously folding domains,which operate cooperatively in the PKS assemblies to synthesize specific polyketide scaffolds.Any nonreactive intermediates tether...Polyketide synthases(PKSs)are megasynthases with multiple autonomously folding domains,which operate cooperatively in the PKS assemblies to synthesize specific polyketide scaffolds.Any nonreactive intermediates tethered to acyl carrier protein(ACP)domain in the PKS will block the elongation process of polyketide chains.In this study,we systematically elucidate the editing function of fungal typeⅡthioesterases(TEIIs)to hydrolyze ACP domain-bounded nonreactive acyl groups,which are uploaded by substrate promiscuous fungal phosphopantetheinyl transferase.Thereof,the TEIIs encoded in gene clusters of nonreducing PKS with reductase domain exhibit universal editing function.Besides,editing function was also found for TEIIs encoded in gene clusters of highly-reducing PKS with condensation domain.Hence,the editing TEIIs with function of recovery PKS are applied to improve the yield of the fungal polyketides in vivo.Our study provides valuable insights into the editing process of fungal PKSs,highlights the crucial role of TEIIs in enhancing polyketide production and introduces a novel metabolic engineering strategy for fungal polyketide biosynthesis by leveraging the editing function of TEIIs.展开更多
(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01....(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01.Their structures were established by extensive spectroscopic analyses,single crystal Xray diffraction,and experimental electronic circular dichroism(ECD)spectra comparison.The plausible biosynthetic pathway of 1 was proposed,which involved the generation of a key spiro[4.5]decane scaffold.Compounds(+)-1a and(-)-1b exhibited significant lipid-lowering activity in 3T3-L1 adipocytes model,with EC50values of 7.85±1.56 and 8.87±0.80μmol/L,respectively.展开更多
Two novel fungal metabolites,asperochones A and B,were obtained from an Aspergillus sp.Their structures were determined by 1D/2D nuclear magnetic resonance(NMR)spectroscopy,high resolution electrospray ionization mass...Two novel fungal metabolites,asperochones A and B,were obtained from an Aspergillus sp.Their structures were determined by 1D/2D nuclear magnetic resonance(NMR)spectroscopy,high resolution electrospray ionization mass spectroscopy(HRESIMS),and single-crystal X-ray diffraction analysis.Asperochone A possesses an intriguing skeleton bearing 5/6/6/6/7/5/5/5 octacyclic ring system,and asperochone B also exhibits an unusual carbon skeleton with five stereochiral centers.Their structures were proposed as heterotrimeric and heterodimeric products of aromatic polyketides.In addition,asperochone A exhibited a potential anti-tuberculosis effect since it showed a moderate potency against Mycobacterium smegmatis.展开更多
Seven novel linear polyketides,talaketides A-G(1-7),were isolated from the rice media cultures of the mangrove sed-iment-derived fungus Talaromyces sp.SCSIO 41027.Among these,talaketides A-E(1-5)represented unpreceden...Seven novel linear polyketides,talaketides A-G(1-7),were isolated from the rice media cultures of the mangrove sed-iment-derived fungus Talaromyces sp.SCSIO 41027.Among these,talaketides A-E(1-5)represented unprecedented unsaturated lin-ear polyketides with an epoxy ring structure.The structures,including absolute configurations of these compounds,were elucidated through detailed analyses of nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HR-MS)data,as well as elec-tronic custom distributors(ECD)calculations.In the cytotoxicity screening against prostate cancer cell lines,talaketide E(5)demon-strated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines,with an IC50 value of 14.44 μmol·L-1.Moreover,com-pound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase,ultimately inducing ap-optosis.These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treat-ment for prostate cancer.展开更多
Three known compounds were isolated from the endophytic fungus Trichoderma sp Xy24 from a mangrove plant Xylocarpus granatum by using various column chromatography techniques. Their structures were identified as harzi...Three known compounds were isolated from the endophytic fungus Trichoderma sp Xy24 from a mangrove plant Xylocarpus granatum by using various column chromatography techniques. Their structures were identified as harzianone （1）, trichoacorenol （2）, and trichodimerol （3） by extensive spectroscopic analysis. Among them, 1 was a harziane diterpene, 2 was a sesquiterpene alcohol, and 3 was a polyketide with a completely symmetric configuration. Compound 3 exhibited medium inhibitory activity with an IC50 value of 74.6 μM using a NA （H7N9）/MUNANA model.展开更多
Fungal aromatic compounds comprise an important and structurally diverse group of secondary metabolites.Several genome sequencing projects revealed many putative biosynthetic gene clusters of fungal aromatic compounds...Fungal aromatic compounds comprise an important and structurally diverse group of secondary metabolites.Several genome sequencing projects revealed many putative biosynthetic gene clusters of fungal aromatic compounds,but many of these genes seem to be silent under typical laboratory culture conditions.To gain access to this untapped reservoir of natural products,we utilized chemical epigenetic modifiers to induce the expression of dormant biosynthetic genes.As a result,the concomitant supplementation of the histone deacetylase inhibitors suberoylanilide hydroxamic acid(500mM)and nicotinamide(50mM)to the culture medium of a fungal pathogen,Stagonospora nodorum,resulted in the isolation of three aromatic compounds(1-3),including a novel natural butyrophenone,(+)-4'-methoxy-(2S)-methylbutyrophenone(1),and two known polyketides,alternariol(2)and(-)-(3R)-mellein methyl ether(3).展开更多
Four new fungal polyketides named koninginins N-Q(1–4),together with four known analogues(5–8),were isolated from the endophytic fungus Trichoderma koningiopsis YIM PH30002 harbored in Panax notoginseng.Their struct...Four new fungal polyketides named koninginins N-Q(1–4),together with four known analogues(5–8),were isolated from the endophytic fungus Trichoderma koningiopsis YIM PH30002 harbored in Panax notoginseng.Their structures were determined on the basis of spectral data interpretation.These compounds were evaluated for their antifungal activity,nitric oxide inhibition,and anticoagulant activity.展开更多
Polyketides have been widely used clinically due to their significant biological activities, but the needed structural and functional diversity cannot be achieved by common chemical synthetic methods. The tool of comb...Polyketides have been widely used clinically due to their significant biological activities, but the needed structural and functional diversity cannot be achieved by common chemical synthetic methods. The tool of combinatorial biosynthesis provides the possibility to produce "unnatural" natural drugs, which has achieved initial success. This paper provides an overview for the strategies of combinatorial biosynthesis in producing the structural and functional diversity of polyketides, including the redesign of metabolic flow, polyketide synthase(PKS) engineering, and PKS post-translational modification. Although encouraging progress has been made in the last decade, challenges still exist regarding the rational combinatorial biosynthesis of polyketides. In this review, the perspectives of polyketide combinatorial biosynthesis are also discussed.展开更多
Two new isomeric modified tripeptides,aspergillamides C and D(compounds 1 and 2),together with fifteen known compounds(compounds 3-17),were obtained from the marine sponge-derived fungus Aspergillus terreus SCSIO 4100...Two new isomeric modified tripeptides,aspergillamides C and D(compounds 1 and 2),together with fifteen known compounds(compounds 3-17),were obtained from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008.The structures of the new compounds,including absolute configurations,were determined by extensive analyses of spectroscopic data(NMR,MS,UV,and IR)and comparisons between the calculated and experimental electronic circular dichroism(ECD)spectra.Butyrolactone I(compound 11)exhibited strong inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B(MptpB)with the IC_(50) being 5.11±0.53μmol·L^(–1),and acted as a noncompetitive inhibitor based on kinetic analysis.展开更多
The diversity of modular polyketide synthase （PKS） genes in sediments of Ardley Island in Antarctica, was studied by restriction fragment length polymorphism （RFLP） analysis. Phylogenetic analysis of 14 amino acid...The diversity of modular polyketide synthase （PKS） genes in sediments of Ardley Island in Antarctica, was studied by restriction fragment length polymorphism （RFLP） analysis. Phylogenetic analysis of 14 amino acid （AA） sequences indicates that the identified ketosynthase （KS） domains were clustered with those from diverse bacterial groups, including Cyanobacteria, γ-Proteobacteria, Actinobacteria, Firmicutes, and some unidentified microorganisms from marine sponge, bryozoan and other environmental samples. The obtained KS domains showed 43%–81% similarity at the AA level to reference sequences in GenBank. Six identified KS domains showed diverse sequences of the motif （VQTACSTS） that was used to identify the hybrid PKS/nonribosomal peptide synthetase （NRPS） enzyme complex, and formed a new branch. These results reveal a high diversity and novelty of PKS genes in antarctic sediments.展开更多
Squamostatin-B (1), a new polyketide or acetogenin, has been isolated from Annona squamosa L. (Annonaceae). Its structure and relative atereochemistry were elucidated on the basis of the spectral analyses of 1 and its...Squamostatin-B (1), a new polyketide or acetogenin, has been isolated from Annona squamosa L. (Annonaceae). Its structure and relative atereochemistry were elucidated on the basis of the spectral analyses of 1 and its derivatives, the acetate (2) and mesitoate (3).展开更多
Eight new furan derivatives,irpexins A‒H(1‒8),two new polyketides,irpexins I and J(9 and 10),together with nine known compounds were isolated from the fermentation of Irpex lacteus.The structures and absolute configur...Eight new furan derivatives,irpexins A‒H(1‒8),two new polyketides,irpexins I and J(9 and 10),together with nine known compounds were isolated from the fermentation of Irpex lacteus.The structures and absolute configurations were elucidated on the basis of extensive spectroscopic methods and Mosher ester reaction.All compounds shows no cytotoxicity to human MCF-7 and Hela cancer cell lines at the concentration of 10μM.展开更多
A novel polyketide pigment （1） with the 4＇,10-coupled linkage between 1-naphthalenol and 1,4-anthraquinone, named rufoolivacin B together with the known analog rufoolivacin （2）, has been isolated from the fruitin...A novel polyketide pigment （1） with the 4＇,10-coupled linkage between 1-naphthalenol and 1,4-anthraquinone, named rufoolivacin B together with the known analog rufoolivacin （2）, has been isolated from the fruiting bodies of the Chinese toadstool Cortinarius rufo-olivaceus （basidiomycetes）. Their structures were characterized by means of analysis of spectroscopic methods, including 2D-NMR experiments and HR-ESI-MS.展开更多
Five new polyketides,craterellones A-E(1-5),were isolated from cultures of basidiomycete Craterellus odoratus,together with five known compounds(6-10).Structures of 1-5 were elucidated on the basis of extensive spectr...Five new polyketides,craterellones A-E(1-5),were isolated from cultures of basidiomycete Craterellus odoratus,together with five known compounds(6-10).Structures of 1-5 were elucidated on the basis of extensive spectroscopic analysis.All compounds were evaluated for their inhibitory activities against one isozyme of 11β-hydroxysteroid dehydrogenase(11β-HSD1)and cytotoxic activities on five tumor cell lines.Compound 10 exhibited significant cytotoxicity against HL-60,SMMC-7721,A-549,MCF-7,and SW-480,with IC50 values of 0.50,0.69,0.64,1.10,0.54μM,respectively.展开更多
Four polycyclic ten-membered lactones possessing unprecedented 10/6/5 tricyclic ring skeleton,named eutypetides A—D(1—4),and an intriguing polyketide containing a hexahydroisobenzofuran-1(3H)-one motif,named eutypet...Four polycyclic ten-membered lactones possessing unprecedented 10/6/5 tricyclic ring skeleton,named eutypetides A—D(1—4),and an intriguing polyketide containing a hexahydroisobenzofuran-1(3H)-one motif,named eutypetide E(5)were isolated from the marine-derived fungus Eutypella sp.F0219,together with three new related biosynthetic polyketides eutypetides F—H(6—8).The absolute configurations of 1—5 were unequivocally determined by single-crystal X-ray diffraction analyses(Cu Kα),modified Mosher's method and electronic circular dichroism(ECD)calculations.Eutypetides G(7)showed remarkable anti-inflammatory activity and could reduce the mRNA expression of proinflammatory cytokines IL-1β,IL-6,TNF-α,and iNOS induced by LPS.Most notably,compounds 1—4 were formed biogenetically from 6—7 via the key intramolecular[4+2]cycloaddition,while compound 5 could be constructed biogenetically from 8 through the intramolecular[4+2]cycloaddition.All the above eight polyketides are proposed to originate from a C10 and a C6 fatty acid.展开更多
Spinosyns are natural broad-spectrum biological insecticides with a double glycosylated polyketide structure that are produced by aerobic fermentation of the actinomycete,Saccharopolyspora spinosa.However,their large-...Spinosyns are natural broad-spectrum biological insecticides with a double glycosylated polyketide structure that are produced by aerobic fermentation of the actinomycete,Saccharopolyspora spinosa.However,their large-scale overproduction is hindered by poorly understood bottlenecks in optimizing the original strain,and poor adaptability of the heterologous strain to the production of spinosyn.In this study,we genetically engineered heterologous spinosyn-producer Streptomyces albus J1074 and optimized the fermentation to improve the production of spinosad(spinosyn A and spinosyn D)based on our previous work.We systematically investigated the result of overexpressing polyketide synthase genes(spnA,B,C,D,E)using a constitutive promoter on the spinosad titer in S.albus J1074.The supply of polyketide synthase precursors was then increased to further improve spinosad production.Finally,increasing or replacing the carbon source of the culture medium resulted in a final spinosad titer of~70 mg/L,which is the highest titer of spinosad achieved in heterologous Streptomyces species.This research provides useful strategies for efficient heterologous production of natural products.展开更多
Metabolic engineering efforts toward rewiring metabolism of cells to produce new compounds often require the utilization of non-native enzymatic machinery that is capable of producing a broad range of chemical functio...Metabolic engineering efforts toward rewiring metabolism of cells to produce new compounds often require the utilization of non-native enzymatic machinery that is capable of producing a broad range of chemical functionalities.Polyketides encompass one of the largest classes of chemically diverse natural products.With thousands of known polyketides,modular polyketide synthases(PKSs)share a particularly attractive biosynthetic logic for generating chemical diversity.The engineering of modular PKSs could open access to the deliberate production of both existing and novel compounds.In this review,we discuss PKS engineering efforts applied at both the protein and cellular level for the generation of a diverse range of chemical structures,and we examine future applications of PKSs in the production of medicines,fuels and other industrially relevant chemicals.展开更多
The euglenatides are a family of hybrid polyketide-nonribosomal peptides produced by the unicellular algae Euglena gracilis.These compounds have antiproliferative activity against fungal pathogensand mammalian cancer ...The euglenatides are a family of hybrid polyketide-nonribosomal peptides produced by the unicellular algae Euglena gracilis.These compounds have antiproliferative activity against fungal pathogensand mammalian cancer cell lines.Analysis of E.gracilis extracts revealed that the algae produce not only the euglenatides,but also a corresponding family of analogs that have the same molecular weights as the euglenatides,but are lacking the characteristic triene chromophore.In comparison to the euglenatides,the activity of these analogs is greatly reduced in a mammalian cytotoxicity assay,indicating that the triene is critical to the biological activity of the euglenatides.展开更多
基金supported by the National Key Research and Development Program of China(No.2021YFA0910500)the National Natural Science Foundation of China(Nos.U22A20380,82173706,and 82104028)the Science and Technology Major Project of Hubei Province(No.2021ACA012).
文摘(±)-Talapyrones A−F(1−6),six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems,were isolated from the fungus Talaromyces adpressus.Their structures were determined by spectroscopic analysis and HR-ESI-MS data,and their absolute configurations were elucidated using a modified Mosher’s method and electronic circular dichroism(ECD)calculations.(±)-Talapyrones A−F(1−6)possess a 6/6/6 tricyclic skeleton,presumably formed through a Michael addition reaction between one molecule ofα-pyrone derivative and one molecule of C8 poly-β-keto chain.In addition,compounds 2/3 and 4/5 are two pairs of C-18 epimers,respectively.Putative biosynthetic pathways of 1−6 were discussed.
基金supported by the Natural Science Foundation of China(No.22267001)the Program for Innovative Research Team of Yunnan Province(No.202105AE160006)+5 种基金the Science and Technology Project of Yunnan Province(Nos.202201AT070225,202301AU070217)Yunnan University“Double First-Class”Construction Joint Project(No.202201BF070001-014)Basic Research Plan of Yunnan Provincial Science and Technology Department-Kunming Medical University(No.202301AY070001-186)Project of Yunnan Characteristic Plant Screening and R&D Service CXO Platform(No.2022YKZY001)Key Laboratory of Chemistry in Ethnic Medicinal Resources,State Ethnic Affairs Commission&Ministry of Education,Yunnan Minzu University(No.MZY2205)he Program Innovative Research Team in Science and Technology in Kunming Medical University(No.CXTD202202)。
文摘Three novel,highly oxygenated polyketides,multioketides A-C(1-3),and three previously described multioxidized aromatic polyketides(4-6),were isolated from an endophytic Penicillium sp.YUD17006 associated with Gastrodia elata.Their chem-ical structures were elucidated using extensive spectroscopic data,electronic circular dichroism calculations,and single X-ray diffrac-tion analysis.All metabolites were characterized by a typical α,β-unsaturated ketone fragment and exhibited a high degree of oxidation.Multioketides A and B were identified as a pair of epimers featuring a rare dihydroisobenzofuranone core.Multioketide C possessed a novel 5/6/6/6 heterotetracyclic chemical architecture with unusual 1,4-dioxin functionalities.Plausible biosynthetic pathways for 1-6 were proposed.Additionally,compound 3 demonstrated weak inhibitory activities against both acetylcholinesterase and protein tyr-osine phosphatase 1B.
基金supported financially by the National Natural Science Foundation of China(Nos.82225042,T2192973)the CAMS Innovation Fund for Medical Sciences(No.CIFMS 2021-I2M1-029)。
文摘Polyketide synthases(PKSs)are megasynthases with multiple autonomously folding domains,which operate cooperatively in the PKS assemblies to synthesize specific polyketide scaffolds.Any nonreactive intermediates tethered to acyl carrier protein(ACP)domain in the PKS will block the elongation process of polyketide chains.In this study,we systematically elucidate the editing function of fungal typeⅡthioesterases(TEIIs)to hydrolyze ACP domain-bounded nonreactive acyl groups,which are uploaded by substrate promiscuous fungal phosphopantetheinyl transferase.Thereof,the TEIIs encoded in gene clusters of nonreducing PKS with reductase domain exhibit universal editing function.Besides,editing function was also found for TEIIs encoded in gene clusters of highly-reducing PKS with condensation domain.Hence,the editing TEIIs with function of recovery PKS are applied to improve the yield of the fungal polyketides in vivo.Our study provides valuable insights into the editing process of fungal PKSs,highlights the crucial role of TEIIs in enhancing polyketide production and introduces a novel metabolic engineering strategy for fungal polyketide biosynthesis by leveraging the editing function of TEIIs.
基金National Natural Science Foundation of China(Nos.U20A2001,81973195,21877133)the Guangdong Marine Economy Development Special Project(Nos.GDNRC[2022]35,GDNRC[2023]39)。
文摘(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01.Their structures were established by extensive spectroscopic analyses,single crystal Xray diffraction,and experimental electronic circular dichroism(ECD)spectra comparison.The plausible biosynthetic pathway of 1 was proposed,which involved the generation of a key spiro[4.5]decane scaffold.Compounds(+)-1a and(-)-1b exhibited significant lipid-lowering activity in 3T3-L1 adipocytes model,with EC50values of 7.85±1.56 and 8.87±0.80μmol/L,respectively.
基金supported by the National Natural Science Foundation of China(No.32170403)the 111 Center from Ministry of Education of China and the State Administration of Foreign Experts Affairs of China(No.B18056)+1 种基金the“Double First-Class”University Project(No.CPU2018GF03)the Drug Innovation Major Project(Nos.2018ZX09711-001-007 and 2018ZX09735002-003)。
文摘Two novel fungal metabolites,asperochones A and B,were obtained from an Aspergillus sp.Their structures were determined by 1D/2D nuclear magnetic resonance(NMR)spectroscopy,high resolution electrospray ionization mass spectroscopy(HRESIMS),and single-crystal X-ray diffraction analysis.Asperochone A possesses an intriguing skeleton bearing 5/6/6/6/7/5/5/5 octacyclic ring system,and asperochone B also exhibits an unusual carbon skeleton with five stereochiral centers.Their structures were proposed as heterotrimeric and heterodimeric products of aromatic polyketides.In addition,asperochone A exhibited a potential anti-tuberculosis effect since it showed a moderate potency against Mycobacterium smegmatis.
基金supported by the Key-Area Research and Development Program of Guangdong Province(No.2023B1111050008)the National Natural Science Foundation of China(Nos.U23A20528,U20A20101)+1 种基金Guangdong Local Innovation Team Program(No.2019BT02Y262)the Postdoctoral Fellowship Program of CPSF(No.GZC20232777).
文摘Seven novel linear polyketides,talaketides A-G(1-7),were isolated from the rice media cultures of the mangrove sed-iment-derived fungus Talaromyces sp.SCSIO 41027.Among these,talaketides A-E(1-5)represented unprecedented unsaturated lin-ear polyketides with an epoxy ring structure.The structures,including absolute configurations of these compounds,were elucidated through detailed analyses of nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HR-MS)data,as well as elec-tronic custom distributors(ECD)calculations.In the cytotoxicity screening against prostate cancer cell lines,talaketide E(5)demon-strated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines,with an IC50 value of 14.44 μmol·L-1.Moreover,com-pound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase,ultimately inducing ap-optosis.These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treat-ment for prostate cancer.
基金Science&Technology Project of Guangdong Province(Grant No.2011A080403020)the Fundamental Research Funds for the Central Universities(Grant No.2012N06)
文摘Three known compounds were isolated from the endophytic fungus Trichoderma sp Xy24 from a mangrove plant Xylocarpus granatum by using various column chromatography techniques. Their structures were identified as harzianone （1）, trichoacorenol （2）, and trichodimerol （3） by extensive spectroscopic analysis. Among them, 1 was a harziane diterpene, 2 was a sesquiterpene alcohol, and 3 was a polyketide with a completely symmetric configuration. Compound 3 exhibited medium inhibitory activity with an IC50 value of 74.6 μM using a NA （H7N9）/MUNANA model.
基金This work was financially supported by Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology,Japan,and by programs from the National Natural Science Foundation Province of China(21202033)the Natural Science Foundation of Hebei(C2012201047)the Foundation of Hebei University(179).
文摘Fungal aromatic compounds comprise an important and structurally diverse group of secondary metabolites.Several genome sequencing projects revealed many putative biosynthetic gene clusters of fungal aromatic compounds,but many of these genes seem to be silent under typical laboratory culture conditions.To gain access to this untapped reservoir of natural products,we utilized chemical epigenetic modifiers to induce the expression of dormant biosynthetic genes.As a result,the concomitant supplementation of the histone deacetylase inhibitors suberoylanilide hydroxamic acid(500mM)and nicotinamide(50mM)to the culture medium of a fungal pathogen,Stagonospora nodorum,resulted in the isolation of three aromatic compounds(1-3),including a novel natural butyrophenone,(+)-4'-methoxy-(2S)-methylbutyrophenone(1),and two known polyketides,alternariol(2)and(-)-(3R)-mellein methyl ether(3).
基金This work was supported partly by grants from the National Natural Science Foundation of China(Nos.81360480,21262041 and 81460536).
文摘Four new fungal polyketides named koninginins N-Q(1–4),together with four known analogues(5–8),were isolated from the endophytic fungus Trichoderma koningiopsis YIM PH30002 harbored in Panax notoginseng.Their structures were determined on the basis of spectral data interpretation.These compounds were evaluated for their antifungal activity,nitric oxide inhibition,and anticoagulant activity.
基金supported by the Major Research Plan of Tianjin(No.16YFXTSF00460)
文摘Polyketides have been widely used clinically due to their significant biological activities, but the needed structural and functional diversity cannot be achieved by common chemical synthetic methods. The tool of combinatorial biosynthesis provides the possibility to produce "unnatural" natural drugs, which has achieved initial success. This paper provides an overview for the strategies of combinatorial biosynthesis in producing the structural and functional diversity of polyketides, including the redesign of metabolic flow, polyketide synthase(PKS) engineering, and PKS post-translational modification. Although encouraging progress has been made in the last decade, challenges still exist regarding the rational combinatorial biosynthesis of polyketides. In this review, the perspectives of polyketide combinatorial biosynthesis are also discussed.
基金supported by the National Natural Science Foundation of China(Nos.41476135,21772210,and 81741154)Guangdong Special Support Projects(Leading talent for LIU Yong-Hong,and Young talent for ZHOU Xue-Feng)
文摘Two new isomeric modified tripeptides,aspergillamides C and D(compounds 1 and 2),together with fifteen known compounds(compounds 3-17),were obtained from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008.The structures of the new compounds,including absolute configurations,were determined by extensive analyses of spectroscopic data(NMR,MS,UV,and IR)and comparisons between the calculated and experimental electronic circular dichroism(ECD)spectra.Butyrolactone I(compound 11)exhibited strong inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B(MptpB)with the IC_(50) being 5.11±0.53μmol·L^(–1),and acted as a noncompetitive inhibitor based on kinetic analysis.
基金The National Natural Science Foundation of China under contract No.40406029China Ocean Mineral Resources Research & Development Association Funds under contract No.DYXM-115-02-2-04
文摘The diversity of modular polyketide synthase （PKS） genes in sediments of Ardley Island in Antarctica, was studied by restriction fragment length polymorphism （RFLP） analysis. Phylogenetic analysis of 14 amino acid （AA） sequences indicates that the identified ketosynthase （KS） domains were clustered with those from diverse bacterial groups, including Cyanobacteria, γ-Proteobacteria, Actinobacteria, Firmicutes, and some unidentified microorganisms from marine sponge, bryozoan and other environmental samples. The obtained KS domains showed 43%–81% similarity at the AA level to reference sequences in GenBank. Six identified KS domains showed diverse sequences of the motif （VQTACSTS） that was used to identify the hybrid PKS/nonribosomal peptide synthetase （NRPS） enzyme complex, and formed a new branch. These results reveal a high diversity and novelty of PKS genes in antarctic sediments.
基金Project supported by National Natural Science Foundation of China.
文摘Squamostatin-B (1), a new polyketide or acetogenin, has been isolated from Annona squamosa L. (Annonaceae). Its structure and relative atereochemistry were elucidated on the basis of the spectral analyses of 1 and its derivatives, the acetate (2) and mesitoate (3).
基金This work was financially supported by the joint research project from the National Natural Science Foundation of China(Grant No.21961142008)Thailand Research Fund(Grant No.DBG6280008).
文摘Eight new furan derivatives,irpexins A‒H(1‒8),two new polyketides,irpexins I and J(9 and 10),together with nine known compounds were isolated from the fermentation of Irpex lacteus.The structures and absolute configurations were elucidated on the basis of extensive spectroscopic methods and Mosher ester reaction.All compounds shows no cytotoxicity to human MCF-7 and Hela cancer cell lines at the concentration of 10μM.
基金supported by the National Natural Science Foundation of China(No.30670221)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry of China and by the Program for New Century Excellent Talents in University(No.NCET-05-0852)supported by the National Financial Aid for Studying Abroad(No.2007103088)(J.-C.Q.)
文摘A novel polyketide pigment （1） with the 4＇,10-coupled linkage between 1-naphthalenol and 1,4-anthraquinone, named rufoolivacin B together with the known analog rufoolivacin （2）, has been isolated from the fruiting bodies of the Chinese toadstool Cortinarius rufo-olivaceus （basidiomycetes）. Their structures were characterized by means of analysis of spectroscopic methods, including 2D-NMR experiments and HR-ESI-MS.
基金supported by National Basic Research Program of China(973 Program,2009CB522300)the National Natural Science Foundation of China(30830113,U1132607).
文摘Five new polyketides,craterellones A-E(1-5),were isolated from cultures of basidiomycete Craterellus odoratus,together with five known compounds(6-10).Structures of 1-5 were elucidated on the basis of extensive spectroscopic analysis.All compounds were evaluated for their inhibitory activities against one isozyme of 11β-hydroxysteroid dehydrogenase(11β-HSD1)and cytotoxic activities on five tumor cell lines.Compound 10 exhibited significant cytotoxicity against HL-60,SMMC-7721,A-549,MCF-7,and SW-480,with IC50 values of 0.50,0.69,0.64,1.10,0.54μM,respectively.
基金supported by the National Natural Science Foundation of China(82204275,82160653,and 22267006)Natural Science Foundation of Hainan Province(323Ms014 and 222QN303)Fundamental Research Funds for Hainan University(KYQD(ZR)-22088 and KYQD(ZR)-21089)。
文摘Four polycyclic ten-membered lactones possessing unprecedented 10/6/5 tricyclic ring skeleton,named eutypetides A—D(1—4),and an intriguing polyketide containing a hexahydroisobenzofuran-1(3H)-one motif,named eutypetide E(5)were isolated from the marine-derived fungus Eutypella sp.F0219,together with three new related biosynthetic polyketides eutypetides F—H(6—8).The absolute configurations of 1—5 were unequivocally determined by single-crystal X-ray diffraction analyses(Cu Kα),modified Mosher's method and electronic circular dichroism(ECD)calculations.Eutypetides G(7)showed remarkable anti-inflammatory activity and could reduce the mRNA expression of proinflammatory cytokines IL-1β,IL-6,TNF-α,and iNOS induced by LPS.Most notably,compounds 1—4 were formed biogenetically from 6—7 via the key intramolecular[4+2]cycloaddition,while compound 5 could be constructed biogenetically from 8 through the intramolecular[4+2]cycloaddition.All the above eight polyketides are proposed to originate from a C10 and a C6 fatty acid.
基金This work was supported by the National Key R&D Program of China[grant number 2018YFA0900400]the National Natural Science Foundation of China[grant number 31670090],and J1 Biotech Co.,Ltd.
文摘Spinosyns are natural broad-spectrum biological insecticides with a double glycosylated polyketide structure that are produced by aerobic fermentation of the actinomycete,Saccharopolyspora spinosa.However,their large-scale overproduction is hindered by poorly understood bottlenecks in optimizing the original strain,and poor adaptability of the heterologous strain to the production of spinosyn.In this study,we genetically engineered heterologous spinosyn-producer Streptomyces albus J1074 and optimized the fermentation to improve the production of spinosad(spinosyn A and spinosyn D)based on our previous work.We systematically investigated the result of overexpressing polyketide synthase genes(spnA,B,C,D,E)using a constitutive promoter on the spinosad titer in S.albus J1074.The supply of polyketide synthase precursors was then increased to further improve spinosad production.Finally,increasing or replacing the carbon source of the culture medium resulted in a final spinosad titer of~70 mg/L,which is the highest titer of spinosad achieved in heterologous Streptomyces species.This research provides useful strategies for efficient heterologous production of natural products.
基金This work was funded by the Joint BioEnergy Institute(JBEI),which is funded by the U.S.Department of Energy,Office of Science,Office of Biological and Environmental Research,under Contract DE-AC02-05CH11231by the National Science Foundation under awards MCB-1442724,NSF-GRFP DGE-1106400 and CBET-1437775+1 种基金as part of the Co-Optimization of Fuels&Engines(Co-Optima)project sponsored by the U.S.Department of Energy(DOE)Office of Energy Efficiency and Renewable Energy(EERE)Bioenergy Technologies and Vehicle Technologies Offices,and by the DOE Agile-Biofoundry(https://agilebiofoundry.org)supported by the U.S.Department of Energy,Energy Efficiency and Renewable Energy,Bioenergy Technologies Office,through contract DE-AC02-05CH11231 between Lawrence Berkeley National Laboratory and the U.S.Department of Energy.The United States Government retains and the publisher,by accepting the article for publication,acknowledges that the United States Government retains a nonexclusive,paid-up,irrevocable,world-wide license to publish or reproduce the published form of this manuscript,or allowothers to do so,for United States Government purposes.Additional funding was provided by the National Science Foundation Graduate Research Fellowship under Grant No.(DGE 1106400).
文摘Metabolic engineering efforts toward rewiring metabolism of cells to produce new compounds often require the utilization of non-native enzymatic machinery that is capable of producing a broad range of chemical functionalities.Polyketides encompass one of the largest classes of chemically diverse natural products.With thousands of known polyketides,modular polyketide synthases(PKSs)share a particularly attractive biosynthetic logic for generating chemical diversity.The engineering of modular PKSs could open access to the deliberate production of both existing and novel compounds.In this review,we discuss PKS engineering efforts applied at both the protein and cellular level for the generation of a diverse range of chemical structures,and we examine future applications of PKSs in the production of medicines,fuels and other industrially relevant chemicals.
基金supported by a grant from the National Institutes of Health(R35 GM144076 to R.A.B.).
文摘The euglenatides are a family of hybrid polyketide-nonribosomal peptides produced by the unicellular algae Euglena gracilis.These compounds have antiproliferative activity against fungal pathogensand mammalian cancer cell lines.Analysis of E.gracilis extracts revealed that the algae produce not only the euglenatides,but also a corresponding family of analogs that have the same molecular weights as the euglenatides,but are lacking the characteristic triene chromophore.In comparison to the euglenatides,the activity of these analogs is greatly reduced in a mammalian cytotoxicity assay,indicating that the triene is critical to the biological activity of the euglenatides.
