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Cloning and Elucidation of the FR901464 Gene Cluster Revealing a Complex Acyltransferase-less Polyketide Synthase Using Glycerate as Starter Units
其他题名克隆与解析FR901464的生物合成基因簇发现一个复杂的"AT-less"聚酮合酶以甘油为起始单元
Zhang F(张凤); He HY(贺海燕); Tang MC(唐满成); Tang YM(唐玉敏); Zhou Q(周强); Tang GL(唐功利)
2011
发表期刊J. Am. Chem. Soc.
ISSN0002-7863
卷号133期号:8页码:2452-2462
摘要FR901464, an antitumor natural product, represents a new class of potent anticancer small molecules targeting spliceosome and inhibiting both splicing and nuclear retention of pre-mRNA. Herein we describe the biosynthetic gene cluster of FR901464, identified by degenerate primer PCR amplification of a gene encoding the 3-hydroxy-3-methylglutaryl-CoA synthase (HCS) postulated to be involved in the biosynthesis of a beta-branched polyketide from Pseudomonas sp. No. 2663. This cluster consists of twenty open reading frames (ORFs) and was localized to 93-kb DNA segment, and its involvement in FR901464 biosynthesis was confirmed by gene inactivation and complementation. FR901464 is biosynthesized by a hybrid polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS), HCS, and acyltransferases (AT)-less system. The PKS/NRPS modules feature unusual domain organization including multiple domain redundancy, inactivation, and tandem. Biochemical characterization of a glyceryl transferase and an acyl carrier protein (ACP) in the start module revealed that it incorporates D-1,3-bisphosphoglycerate, which is dephosphorylated and transferred to ACP as the starter unit. Furthermore, an oxidative Baeyer Villiger reaction followed by chain release was postulated to form a pyran moiety. On the basis of in silico analysis and genetic and biochemical evidances, a biosynthetic pathway for FR901464 was proposed, which sets the stage to further investigate the complex PKS biochemically and engineer the biosynthetic machinery for the production of novel analogues.
学科领域生命有机化学
部门归属中科院上海有机化学研究所
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收录类别SCI
语种英语
WOS记录号WOS:000288291300029
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被引频次:27[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/331003/28467
专题生命有机化学国家重点实验室
通讯作者Tang GL(唐功利)
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GB/T 7714
Zhang F,He HY,Tang MC,et al. Cloning and Elucidation of the FR901464 Gene Cluster Revealing a Complex Acyltransferase-less Polyketide Synthase Using Glycerate as Starter Units[J]. J. Am. Chem. Soc.,2011,133(8):2452-2462.
APA 张凤,贺海燕,唐满成,唐玉敏,周强,&唐功利.(2011).Cloning and Elucidation of the FR901464 Gene Cluster Revealing a Complex Acyltransferase-less Polyketide Synthase Using Glycerate as Starter Units.J. Am. Chem. Soc.,133(8),2452-2462.
MLA 张凤,et al."Cloning and Elucidation of the FR901464 Gene Cluster Revealing a Complex Acyltransferase-less Polyketide Synthase Using Glycerate as Starter Units".J. Am. Chem. Soc. 133.8(2011):2452-2462.
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