Cloning and Elucidation of the FR901464 Gene Cluster Revealing a Complex Acyltransferase-less Polyketide Synthase Using Glycerate as Starter Units

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	Cloning and Elucidation of the FR901464 Gene Cluster Revealing a Complex Acyltransferase-less Polyketide Synthase Using Glycerate as Starter Units
	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)
刊名	J. Am. Chem. Soc.
	2011
卷号	133 期号:8 页码:2452-2462
ISSN号	0002-7863
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
通讯作者	唐功利
英文摘要	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.
学科主题	生命有机化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1021/ja105649g
语种	英语
WOS记录号	WOS:000288291300029
公开日期	2013-08-23
内容类型	期刊论文
源URL	[http://202.127.28.38/handle/331003/28467]
专题	上海有机化学研究所_生命有机化学国家重点实验室
推荐引用方式 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.