I型聚酮合酶中酰基转移酶结构域的研究进展

doi:10.6023/cjoc201806016

有机化学 ›› 2018, Vol. 38 ›› Issue (9): 2377-2385.DOI: 10.6023/cjoc201806016 上一篇下一篇

所属专题：合成科学

综述与进展

I型聚酮合酶中酰基转移酶结构域的研究进展

沈洁洁^a,b, 毛旭明^a,b, 陈新爱^a,b, 李永泉^a,b

a 浙江大学药物生物技术研究所杭州 310058;
b 浙江省微生物生化与代谢工程重点实验室杭州 310058

收稿日期:2018-06-12 修回日期:2018-06-29 发布日期:2018-07-16
通讯作者: 李永泉 E-mail:lyq@zju.edu.cn
基金资助:
国家自然科学基金（Nos.3173002，31520103901，31470212，31571284）资助项目.

Recent Advances in Acyltransferase Domain of Type I Polyktide Synthases

Shen Jiejie^a,b, Mao Xuming^a,b, Chen Xin'ai^a,b, Li Yongquan^a,b

a Institute of Pharmaceutical Biotechnology, Zhejiang University, Hangzhou 310058;
b Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou 310058

Received:2018-06-12 Revised:2018-06-29 Published:2018-07-16
Contact: 10.6023/cjoc201806016 E-mail:lyq@zju.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 3173002, 31520103901, 31470212, 31571284).

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摘要/Abstract

大部分抗生素、抗肿瘤、免疫抑制等天然药物是由I型聚酮合酶（PKS）合成的聚酮化合物.I型PKS是以模块形式存在的复合酶，其内每个模块含有多个催化功能域，每个模块负责完成一次链延伸反应.总结了近年I型PKS中催化功能域酰基转移酶（AT）的相关研究，分析了AT结构域的种类、转运多样性的底物、催化机制及其蛋白质结构，并介绍了通过AT结构域的替换、点突变和互补设计新型聚酮衍生物的相关探索，从而阐明AT结构域底物选择性是决定聚酮化合物产物多样性的关键因素之一，为人工构建新型聚酮化合物的高效生物合成路线奠定理论基础.

关键词: AT结构域, 底物专一性, 催化机制, I型PKS, 聚酮化合物

Most polyketide natural compounds, such as antibiotics, antineoplastics and immunosuppressants, are produced by type I polyketide synthases (PKSs). Type I PKSs are composed of several catalytic modules, each of which contains iterative domains, such as acyltransferase (AT) domain, for one round of polyketide chain elongation. The recent advances on AT domains of type I PKS modules and analyzes their categories, the diverse acyl subunits they transfer, their catalytic mechanisms and their protein structures are summarized. Moreover, the recent progress in AT engineering (AT domains swaps, AT site-directed mutagenesis and trans-AT complementation) for new polyketide derivatives is summarized, to show that the substrate specificity of AT domains is one of the key factors on determining the diversity of polyketide backbones. These works have laid a theoretical foundation for the further development of novel polyketides with multi-functions and in high-yields by AT domain engineering.

Key words: AT domain, substrate specificity, catalytic mechanism, type I PKS, polyketide

引用此文

沈洁洁, 毛旭明, 陈新爱, 李永泉. I型聚酮合酶中酰基转移酶结构域的研究进展[J]. 有机化学, 2018, 38(9): 2377-2385.

Shen Jiejie, Mao Xuming, Chen Xin'ai, Li Yongquan. Recent Advances in Acyltransferase Domain of Type I Polyktide Synthases[J]. Chin. J. Org. Chem., 2018, 38(9): 2377-2385.

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I型聚酮合酶中酰基转移酶结构域的研究进展

Recent Advances in Acyltransferase Domain of Type I Polyktide Synthases

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