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 new aromatic polyketides, communols A-G （1-7）, were isolated and identified from the fermentation broth of Penicillium commune 518, a marine-derived fungus associated with the Gorgonian, Muricella abnormalis. ...Seven new aromatic polyketides, communols A-G （1-7）, were isolated and identified from the fermentation broth of Penicillium commune 518, a marine-derived fungus associated with the Gorgonian, Muricella abnormalis. The new structures of 1-7 were determined by spectroscopic analysis and X-ray single crystal diffraction. Among them, communol D （4） was the first example of a naturally occurring aromatic polyketide with a sulfoxide group from marine thngi. Compounds 1, 6, and 7 all showed moderate antimicrobial activities against Escherichia coli and Enterobacter aerogenes with MIC values of 4.1/16.4, 6.4/25.8, and 23.8/23.8μmoloL^-1, respectively.展开更多
The bacterial trialkyl-substituted aromatic polyketides are structurally featured with the unusual aromatic core in the middle of polyketide chain such as TM-123(1),veramycin A(2),NFAT-133(3)and benwamycin I(4),which ...The bacterial trialkyl-substituted aromatic polyketides are structurally featured with the unusual aromatic core in the middle of polyketide chain such as TM-123(1),veramycin A(2),NFAT-133(3)and benwamycin I(4),which were discovered from Streptomyces species and demonstrated with antidiabetic and immunosuppressant activities.Though the biosynthetic pathway of 1-3 was reported as a type I polyketide synthase(PKS),the PKS assembly line was interpreted inconsistently,and it remains a mystery how the compound 3 was generated.Herein,the PKS assembly logic of 1-4 was revised by site-mutagenetic analysis of the PKS dehydratase domains.Based on gene deletion and complementation,the putative P450 monooxygenase nftE1 and metallo-beta-lactamase(MBL)fold hydrolase nftF1 were verified as essential genes for the biosynthesis of 1-4.The absence of nftE1 led to abolishment of 1-4 and accumulation of new products(5-8).Structural elucidation reveals 5-8 as the non-aromatic analogs of 1,suggesting the NftE1-catalyzed aromatic core formation.Deletion of nftF1 resulted in disappearance of 3 and 4 with the compounds 1 and 2 unaffected.As a rare MBL-fold hydrolase from type I PKSs,NftF1 potentially generates the compound 3 through two strategies:catalyze premature chain-offloading as a trans-acting thioesterase or hydrolyze the lactone-bond of compound 1 as an esterase.展开更多
To accelerate the shift to bio-based production and overcome complicated functional implementation of natural and artificial biosynthetic pathways to industry relevant organisms,development of new,versatile,bio-based ...To accelerate the shift to bio-based production and overcome complicated functional implementation of natural and artificial biosynthetic pathways to industry relevant organisms,development of new,versatile,bio-based production platforms is required.Here we present a novel yeast-based platform for biosynthesis of bacterial aromatic polyketides.The platform is based on a synthetic polyketide synthase system enabling a first demonstration of bacterial aromatic polyketide biosynthesis in a eukaryotic host.展开更多
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.
文摘Seven new aromatic polyketides, communols A-G （1-7）, were isolated and identified from the fermentation broth of Penicillium commune 518, a marine-derived fungus associated with the Gorgonian, Muricella abnormalis. The new structures of 1-7 were determined by spectroscopic analysis and X-ray single crystal diffraction. Among them, communol D （4） was the first example of a naturally occurring aromatic polyketide with a sulfoxide group from marine thngi. Compounds 1, 6, and 7 all showed moderate antimicrobial activities against Escherichia coli and Enterobacter aerogenes with MIC values of 4.1/16.4, 6.4/25.8, and 23.8/23.8μmoloL^-1, respectively.
基金the National Natural Science Foundation of China(Nos.32070070,32211530074 and 31929001)the innovative research team of high-level local universities in Shanghai.H.D.thanks Royal Society-NSFC international exchange grant(IEC\NSFC\211349).
文摘The bacterial trialkyl-substituted aromatic polyketides are structurally featured with the unusual aromatic core in the middle of polyketide chain such as TM-123(1),veramycin A(2),NFAT-133(3)and benwamycin I(4),which were discovered from Streptomyces species and demonstrated with antidiabetic and immunosuppressant activities.Though the biosynthetic pathway of 1-3 was reported as a type I polyketide synthase(PKS),the PKS assembly line was interpreted inconsistently,and it remains a mystery how the compound 3 was generated.Herein,the PKS assembly logic of 1-4 was revised by site-mutagenetic analysis of the PKS dehydratase domains.Based on gene deletion and complementation,the putative P450 monooxygenase nftE1 and metallo-beta-lactamase(MBL)fold hydrolase nftF1 were verified as essential genes for the biosynthesis of 1-4.The absence of nftE1 led to abolishment of 1-4 and accumulation of new products(5-8).Structural elucidation reveals 5-8 as the non-aromatic analogs of 1,suggesting the NftE1-catalyzed aromatic core formation.Deletion of nftF1 resulted in disappearance of 3 and 4 with the compounds 1 and 2 unaffected.As a rare MBL-fold hydrolase from type I PKSs,NftF1 potentially generates the compound 3 through two strategies:catalyze premature chain-offloading as a trans-acting thioesterase or hydrolyze the lactone-bond of compound 1 as an esterase.
基金This work was funded by grants from the Novo Nordisk Foundation[NNF10CC1016517],[NNF15OC0016626]and is part of the U.S.Department of Energy Joint BioEnergy Institute supported by the U.S.Department of Energy,Office of Science,Office of Biological and Environmental Research,through Contract DE-AC02-05CH11231 between Lawrence Berkeley National Laboratory and the U.S.Department of Energy.
文摘To accelerate the shift to bio-based production and overcome complicated functional implementation of natural and artificial biosynthetic pathways to industry relevant organisms,development of new,versatile,bio-based production platforms is required.Here we present a novel yeast-based platform for biosynthesis of bacterial aromatic polyketides.The platform is based on a synthetic polyketide synthase system enabling a first demonstration of bacterial aromatic polyketide biosynthesis in a eukaryotic host.
