Cloning and Elucidation of the FR901464 Gene Cluster Revealing a Complex Acyltransferase-less Polyketide Synthase Using Glycerate as Starter Units
文献类型：期刊论文
| 作者 | 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.
 |
| 出版日期 | 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 |
| 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. |
入库方式： OAI收割
来源：上海有机化学研究所
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