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Characterization of the saframycin a gene cluster from Streptomyces lavendulae NRRL 11002 revealing a nonribosomal peptide synthetase system for assembling the unusual tetrapeptidyl skeleton in an iterative manner
其他题名Characterization of the saframycin a gene cluster from Streptomyces lavendulae NRRL 11002 revealing a nonribosomal peptide synthetase system for assembling the unusual tetrapeptidyl skeleton in an iterative manner
Li L(李磊); Deng W(邓玮); Song J(宋杰); Ding W(丁伟); Zhao QF(赵群飞); Peng C(彭超); Song WW(宋玮雯); Tang GL(唐功利); Liu W(刘文)
2008
发表期刊J. Bacteriol.
ISSN0021-9193
卷号190期号:1页码:251-263
摘要Saframycin A (SFM-A), produced by Streptomyces lavendulae NRRL 11002, belongs to the tetrahydroisoquinoline family of antibiotics, and its core is structurally similar to the core of ecteinascidin 743, which is a highly potent antitumor drug isolated from a marine tunicate. In this study, the biosynthetic gene cluster for SFM-A was cloned and localized to a 62-kb contiguous DNA region. Sequence analysis revealed 30 genes that constitute the SFM-A gene cluster, encoding an unusual nonribosomal peptide synthetase (NRPS) system and tailoring enzymes and regulatory and resistance proteins. The results of substrate prediction and in vitro characterization of the adenylation specificities of this NRPS system support the hypothesis that the last module acts in an iterative manner to form a tetrapeptidyl intermediate and that the colinearity rule does not apply. Although this mechanism is different from those proposed for the SFM-A analogs SFM-Mx1 and safracin B (SAC-B), based on the high similarity of these systems, it is likely they share a common mechanism of biosynthesis as we describe here. Construction of the biosynthetic pathway of SFM-Y3, an aminated SFM-A, was achieved in the SAC-B producer (Pseudomonas fluorescens). These findings not only shed new insight on tetrahydroisoquinoline biosynthesis but also demonstrate the feasibility of engineering microorganisms to generate structurally more complex and biologically more active analogs by combinatorial biosynthesis.
学科领域生命有机化学
部门归属中科院上海有机所
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收录类别SCI
语种英语
WOS记录号WOS:000252080400024
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被引频次:74[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.sioc.ac.cn/handle/331003/27727
专题上海有机化学研究所
通讯作者Tang GL(唐功利); Liu W(刘文)
推荐引用方式
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Li L,Deng W,Song J,et al. Characterization of the saframycin a gene cluster from Streptomyces lavendulae NRRL 11002 revealing a nonribosomal peptide synthetase system for assembling the unusual tetrapeptidyl skeleton in an iterative manner[J]. J. Bacteriol.,2008,190(1):251-263.
APA 李磊.,邓玮.,宋杰.,丁伟.,赵群飞.,...&刘文.(2008).Characterization of the saframycin a gene cluster from Streptomyces lavendulae NRRL 11002 revealing a nonribosomal peptide synthetase system for assembling the unusual tetrapeptidyl skeleton in an iterative manner.J. Bacteriol.,190(1),251-263.
MLA 李磊,et al."Characterization of the saframycin a gene cluster from Streptomyces lavendulae NRRL 11002 revealing a nonribosomal peptide synthetase system for assembling the unusual tetrapeptidyl skeleton in an iterative manner".J. Bacteriol. 190.1(2008):251-263.
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