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学科主题: 生命有机化学
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
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
作者: 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)
通讯作者: 唐功利 ; 刘文
刊名: J. Bacteriol.
发表日期: 2008
卷: 190, 期:1, 页:251-263
收录类别: SCI
部门归属: 中科院上海有机所
英文摘要: 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.
语种: 英语
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WOS记录号: WOS:000252080400024
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内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/27727
Appears in Collections:上海有机化学研究所_期刊论文

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Recommended Citation:
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.
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