SIOC OpenIR  > 生命有机化学国家重点实验室
Rational Control of Polyketide Extender Units by Structure-Based Engineering of a Crotonyl-CoA Carboxylase/Reductase in Antimycin Biosynthesis
Alternative Title以结构为基础工程改造抗霉素生物合成中的巴豆酰CoA羧化酶/还原酶以合理控制聚酮的延伸单元
Zhang LH(张骊駻)1; MORI TAKAHIRO1; Zheng QF(郑庆飞)1; AWAKAWA TAKAYOSHI1; Yan Y(闫岩)1; Liu W(刘文)1; ABE IKURO1
2015
Source PublicationAngew. Chem.-Int. Edit.
Volume54Issue:45Pages:13462-13465
AbstractBioengineering of natural product biosynthesis is a powerful approach to expand the structural diversity of bioactive molecules. However, in polyketide biosynthesis, the modification of polyketide extender units, which form the carbon skeletons, has remained challenging. Herein, we report the rational control of polyketide extender units by the structure-based engineering of a crotonyl-CoA carboxylase/reductase (CCR), in the biosynthesis of antimycin. Site-directed mutagenesis of the CCR enzyme AntE, guided by the crystal structure solved at 1.5 angstrom resolution, expanded its substrate scope to afford indolylmethylmalonyl-CoA by the V350G mutation. The mutant A182L selectively catalyzed carboxylation over the regular reduction. Furthermore, the combinatorial biosynthesis of heterocycle- and substituted arene-bearing antimycins was achieved by an engineered Streptomyces strain bearing AntE(V350G). These findings deepen our understanding of the molecular mechanisms of the CCRs, which will serve as versatile biocatalysts for the manipulation of building blocks, and set the stage for the rational design of polyketide biosynthesis.
Subtype论文
Subject Area生命有机化学
DOI10.1002/anie.201506899
URL查看原文
Indexed BySCI
Language英语
WOS IDWOS:000363691500059
Citation statistics
Cited Times:13[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sioc.ac.cn/handle/331003/39532
Collection生命有机化学国家重点实验室
Corresponding AuthorABE IKURO
Affiliation1.日本东京大学
2.中科院上海有机化学研究所, 生命有机化学国家重点实验室
Recommended Citation
GB/T 7714
Zhang LH,MORI TAKAHIRO,Zheng QF,et al. Rational Control of Polyketide Extender Units by Structure-Based Engineering of a Crotonyl-CoA Carboxylase/Reductase in Antimycin Biosynthesis[J]. Angew. Chem.-Int. Edit.,2015,54(45):13462-13465.
APA 张骊駻.,MORI TAKAHIRO.,郑庆飞.,AWAKAWA TAKAYOSHI.,闫岩.,...&ABE IKURO.(2015).Rational Control of Polyketide Extender Units by Structure-Based Engineering of a Crotonyl-CoA Carboxylase/Reductase in Antimycin Biosynthesis.Angew. Chem.-Int. Edit.,54(45),13462-13465.
MLA 张骊駻,et al."Rational Control of Polyketide Extender Units by Structure-Based Engineering of a Crotonyl-CoA Carboxylase/Reductase in Antimycin Biosynthesis".Angew. Chem.-Int. Edit. 54.45(2015):13462-13465.
Files in This Item:
File Name/Size DocType Version Access License
2015544.pdf(1674KB)期刊论文作者接受稿开放获取CC BY-NC-SAApplication Full Text
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[张骊駻]'s Articles
[MORI TAKAHIRO]'s Articles
[郑庆飞]'s Articles
Baidu academic
Similar articles in Baidu academic
[张骊駻]'s Articles
[MORI TAKAHIRO]'s Articles
[郑庆飞]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[张骊駻]'s Articles
[MORI TAKAHIRO]'s Articles
[郑庆飞]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.