Rational Control of Polyketide Extender Units by Structure-Based Engineering of a Crotonyl-CoA Carboxylase/Reductase in Antimycin Biosynthesis

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	Rational Control of Polyketide Extender Units by Structure-Based Engineering of a Crotonyl-CoA Carboxylase/Reductase in Antimycin Biosynthesis
	Zhang LH(张骊駻)1; MORI TAKAHIRO 1; Zheng QF(郑庆飞)1; AWAKAWA TAKAYOSHI 1; Yan Y(闫岩)1; Liu W(刘文)1; ABE IKURO 1
刊名	Angew. Chem.-Int. Edit.
	2015
卷号	54 期号:45 页码:13462-13465
其他题名	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
通讯作者	ABE IKURO
英文摘要	Bioengineering 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.
学科主题	生命有机化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1002/anie.201506899
语种	英语
WOS记录号	WOS:000363691500059
内容类型	期刊论文
源URL	[http://ir.sioc.ac.cn/handle/331003/39532]
专题	上海有机化学研究所_生命有机化学国家重点实验室
作者单位	1.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
推荐引用方式 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.