Structural and Functional Analysis of the Loading Acyltransferase from Avermectin Modular Polyketide Synthase
文献类型：期刊论文
| 作者 | Wang, Fen1; Wang, Yanjie1; Ji, Junjie1; Zhou, Zhan1; Yu, Jingkai1; Zhu, Hua2; Su, Zhiguo1; Zhang, Lixin2; Zheng, Jianting1 |
| 刊名 | ACS Chemical Biology
 |
| 出版日期 | 2015-04-01 |
| 卷号 | 10期号:4页码:1017-1025 |
| ISSN号 | 1554-8929 |
| 英文摘要 | The loading acyltransferase (AT) domains of modular polyketide synthases (PKSs) control the choice of starter units incorporated into polyketides and are therefore attractive targets for the engineering of modular PKSs. Here, we report the structural and biochemical characterizations of the loading AT from avermectin modular PKS, which accepts more than 40 carboxylic acids as alternative starter units for the biosynthesis of a series of congeners. This first structural analysis of loading ATs from modular PKSs revealed the molecular basis for the relaxed substrate specificity. Residues important for substrate binding and discrimination were predicted by modeling a substrate into the active site. A mutant with altered specificity toward a panel of synthetic substrate mimics was generated by site-directed mutagenesis of the active site residues. The hydrolysis of the N-acetylcysteamine thioesters of racemic 2-methylbutyric acid confirmed the stereospecificity of the avermectin loading AT for an S configuration at the C-2 position of the substrate. Together, these results set the stage for region-specific modification of polyketides through active site engineering of loading AT domains of modular PKSs. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 研究领域[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | FATTY-ACID SYNTHASE ; SUBSTRATE-SPECIFICITY ; CRYSTAL-STRUCTURE ; PROTEIN INTERACTIONS ; ACTIVE-SITE ; BIOSYNTHESIS ; DOMAIN ; KETOREDUCTASES ; TRANSACYLASE ; BORRELIDIN |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000353315100014 |
| 公开日期 | 2015-07-08 |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/16735]  |
| 专题 | 过程工程研究所_生化工程国家重点实验室 |
| 作者单位 | 1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Fen,Wang, Yanjie,Ji, Junjie,et al. Structural and Functional Analysis of the Loading Acyltransferase from Avermectin Modular Polyketide Synthase[J]. ACS Chemical Biology,2015,10(4):1017-1025. |
| APA | Wang, Fen.,Wang, Yanjie.,Ji, Junjie.,Zhou, Zhan.,Yu, Jingkai.,...&Zheng, Jianting.(2015).Structural and Functional Analysis of the Loading Acyltransferase from Avermectin Modular Polyketide Synthase.ACS Chemical Biology,10(4),1017-1025. |
| MLA | Wang, Fen,et al."Structural and Functional Analysis of the Loading Acyltransferase from Avermectin Modular Polyketide Synthase".ACS Chemical Biology 10.4(2015):1017-1025. |
入库方式： OAI收割
来源：过程工程研究所
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