Analysis of the secondary metabolite biosynthesis gene cluster(BGC)from marine Streptomyces sp.SNJ102 revealed the presence of a noncanonical nonribosomal peptide synthetase(NRPS),predicted to produce a depsipeptide c...Analysis of the secondary metabolite biosynthesis gene cluster(BGC)from marine Streptomyces sp.SNJ102 revealed the presence of a noncanonical nonribosomal peptide synthetase(NRPS),predicted to produce a depsipeptide compound.The NRPS gene cluster was captured by transformation-associated recombination and heterologously expressed in Streptomyces albus.The production of the new compound was confirmed using high-resolution liquid chromatography-mass spectrometry,and its structure was elucidated using nuclear magnetic resonance spectroscopy.The structure of the new depsipeptide was more similar to the monomeric structure of cyclic depsipeptides derived from fungi than to other Streptomyces-derived dep-sipeptides.In addition,the bacterial depsipeptide,which we named jejumide,showed promising anti-inflammatory activity.These results demonstrate that genome mining and successful heterologous expression of cryptic nonlinear NRPS BGCs from marine bacteria will facilitate the discovery of novel nonribosomal peptides and understanding of the complicated biosynthetic mechanism of nonlinear NRPS.展开更多
The synthesis of a marine cytotoxic cyclic depsipeptide obyanamide has been accomplished. The key steps include assembling liner pentapeptide via Yamaguchi esterification and HATU-promoted ring closing. The structure ...The synthesis of a marine cytotoxic cyclic depsipeptide obyanamide has been accomplished. The key steps include assembling liner pentapeptide via Yamaguchi esterification and HATU-promoted ring closing. The structure of the synthetic sample was identified by ^1H and ^13C NMR, H-H COSY, HMQC, HMBC, and HRESIMS, but appears to be different from that of the marine natural product.展开更多
A bicyclic depsipeptide, chromopeptide A(1), was isolated from a deep-sea-derived bacterium Chromobacterium sp. HS-13-94. Its structure was determined by extensive spectroscopic analysis and by comparison with a relat...A bicyclic depsipeptide, chromopeptide A(1), was isolated from a deep-sea-derived bacterium Chromobacterium sp. HS-13-94. Its structure was determined by extensive spectroscopic analysis and by comparison with a related known compound. The absolute configuration of chromopeptide A was established by X-ray diffraction analysis employing graphite monochromated Mo K_α radiation(λ ? 0.71073 ?) with small Flack parameter 0.03. Chromopeptide A suppressed the proliferation of HL-60, K-562, and Ramos cells with average IC_(50) values of 7.7, 7.0, and 16.5 nmol/L, respectively.展开更多
By using the corresponding L-amino acid sodium as initiator,ε-caprolactone-depsipeptides CL-Ala and CL-Leu were prepared by the reactions ofε-caprolactone(CL)with L-alanine and L-leucine,respec-tively,and p-dioxanon...By using the corresponding L-amino acid sodium as initiator,ε-caprolactone-depsipeptides CL-Ala and CL-Leu were prepared by the reactions ofε-caprolactone(CL)with L-alanine and L-leucine,respec-tively,and p-dioxanone-depsipeptide(PDO-Leu)was prepared by the reaction of p-dioxanone(PDO)with L-leucine.Two poly(ε-caprolactone)oligomers(PCL-Ala and PCL-Leu)of different molecular weights with depsipeptide unit were synthesized by controlling the feed ratio of L-amino acid sodium and CL.The presence of the depsipeptide structure in these obtained products was confirmed by 1H NMR spectra and the molecular weight of the poly(ε-caprolactone)oligomers was measured by gel permeation chromatography(GPC).These products con-tain a hydroxyl group and a carboxyl group in one molecule,which means they could act as bifunctional monomers for further polymerization to prepare high molecular weight polymers.By this way,the depsipeptide unit could be introduced into the polymers and the biodegradation rates of the novel polymers could be well controlled in vivo by the tailored molecular structures.展开更多
Total synthesis of N-methylsansalvamide A was accomplished in solution phase by a convergent approach. An N-Boc-td-depsipepide 6 and a dipeptide ester 10 were prepared in the yield of 89% and 91%, respectively. Cycliz...Total synthesis of N-methylsansalvamide A was accomplished in solution phase by a convergent approach. An N-Boc-td-depsipepide 6 and a dipeptide ester 10 were prepared in the yield of 89% and 91%, respectively. Cyclization of the linear penta-depsipetide was achieved with PyBOP and DIPEA in DMF-CH2C12.展开更多
Asymmetric total synthesis of emericellamide B（9.4%, 17 longest linear steps） is detailed in this report. In this synthetic route, the highly methylated（2R,3R,4S,6S）-3-hydroxy-2,4,6-trimethyldodecanoic acid（HTMD...Asymmetric total synthesis of emericellamide B（9.4%, 17 longest linear steps） is detailed in this report. In this synthetic route, the highly methylated（2R,3R,4S,6S）-3-hydroxy-2,4,6-trimethyldodecanoic acid（HTMD） unit was effectively prepared through the asymmetric methylation, Wittig and Horner–Wadsworth–Emmons reaction. Moreover, pentafluorophenyl diphenylphophinate（FDPP） proved to be an effective condensation reagent for the macrolactamization between C14 and C18.展开更多
基金supported by the Korea Institute of Planning and Evaluation for Technology in Food,Agriculture and For-estry(IPET)through“Crop Viruses and Pests Response Industry Tech-nology Development”Program(No.321110-4)funded by the Ministry of Agriculture,Food and Rural Affairs(MAFRA),National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.2022R1 A2 C3004621)+1 种基金the Ministry of Education(2022R1I1 A1 A01068507)Bio&Medical Technology Develop-ment Program of the NRF funded by MSIT(No.RS-2024-00352229,No.2022M3 A9 F3017371).
文摘Analysis of the secondary metabolite biosynthesis gene cluster(BGC)from marine Streptomyces sp.SNJ102 revealed the presence of a noncanonical nonribosomal peptide synthetase(NRPS),predicted to produce a depsipeptide compound.The NRPS gene cluster was captured by transformation-associated recombination and heterologously expressed in Streptomyces albus.The production of the new compound was confirmed using high-resolution liquid chromatography-mass spectrometry,and its structure was elucidated using nuclear magnetic resonance spectroscopy.The structure of the new depsipeptide was more similar to the monomeric structure of cyclic depsipeptides derived from fungi than to other Streptomyces-derived dep-sipeptides.In addition,the bacterial depsipeptide,which we named jejumide,showed promising anti-inflammatory activity.These results demonstrate that genome mining and successful heterologous expression of cryptic nonlinear NRPS BGCs from marine bacteria will facilitate the discovery of novel nonribosomal peptides and understanding of the complicated biosynthetic mechanism of nonlinear NRPS.
基金the National Natural Science Foundation of China （30572245）.
文摘The synthesis of a marine cytotoxic cyclic depsipeptide obyanamide has been accomplished. The key steps include assembling liner pentapeptide via Yamaguchi esterification and HATU-promoted ring closing. The structure of the synthetic sample was identified by ^1H and ^13C NMR, H-H COSY, HMQC, HMBC, and HRESIMS, but appears to be different from that of the marine natural product.
基金financially supported by the National Marine ‘863’ Project (Nos. 2012AA092105 and 2013AA092902)the National Natural Science Foundation of China (No. 81273430)
文摘A bicyclic depsipeptide, chromopeptide A(1), was isolated from a deep-sea-derived bacterium Chromobacterium sp. HS-13-94. Its structure was determined by extensive spectroscopic analysis and by comparison with a related known compound. The absolute configuration of chromopeptide A was established by X-ray diffraction analysis employing graphite monochromated Mo K_α radiation(λ ? 0.71073 ?) with small Flack parameter 0.03. Chromopeptide A suppressed the proliferation of HL-60, K-562, and Ramos cells with average IC_(50) values of 7.7, 7.0, and 16.5 nmol/L, respectively.
基金financially supported by Program for the New Century Excellent Talents in University“NCET”,Ministry of Education of China,and by the International Cooperation from Ministry of Science and Technology of China(Grant No.2008DFA51170)sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars,Ministry of Education of China.
文摘By using the corresponding L-amino acid sodium as initiator,ε-caprolactone-depsipeptides CL-Ala and CL-Leu were prepared by the reactions ofε-caprolactone(CL)with L-alanine and L-leucine,respec-tively,and p-dioxanone-depsipeptide(PDO-Leu)was prepared by the reaction of p-dioxanone(PDO)with L-leucine.Two poly(ε-caprolactone)oligomers(PCL-Ala and PCL-Leu)of different molecular weights with depsipeptide unit were synthesized by controlling the feed ratio of L-amino acid sodium and CL.The presence of the depsipeptide structure in these obtained products was confirmed by 1H NMR spectra and the molecular weight of the poly(ε-caprolactone)oligomers was measured by gel permeation chromatography(GPC).These products con-tain a hydroxyl group and a carboxyl group in one molecule,which means they could act as bifunctional monomers for further polymerization to prepare high molecular weight polymers.By this way,the depsipeptide unit could be introduced into the polymers and the biodegradation rates of the novel polymers could be well controlled in vivo by the tailored molecular structures.
基金The authors are grateful to The National Natural Science Foundation of China （No.30472074） to The Hebei province Natural Science Foundation （No.B2006000302） for financial support of this work.
文摘Total synthesis of N-methylsansalvamide A was accomplished in solution phase by a convergent approach. An N-Boc-td-depsipepide 6 and a dipeptide ester 10 were prepared in the yield of 89% and 91%, respectively. Cyclization of the linear penta-depsipetide was achieved with PyBOP and DIPEA in DMF-CH2C12.
基金the National Natural Science Foundation of China (Nos. 21472022, 21272041, 21072034)Key Laboratory for Chemical Biology of Fujian Province for financial support
文摘Asymmetric total synthesis of emericellamide B（9.4%, 17 longest linear steps） is detailed in this report. In this synthetic route, the highly methylated（2R,3R,4S,6S）-3-hydroxy-2,4,6-trimethyldodecanoic acid（HTMD） unit was effectively prepared through the asymmetric methylation, Wittig and Horner–Wadsworth–Emmons reaction. Moreover, pentafluorophenyl diphenylphophinate（FDPP） proved to be an effective condensation reagent for the macrolactamization between C14 and C18.
