Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuhan, 430071, P.R. China.
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.
Angew Chem Int Ed Engl. 2017 May 8;56(20):5503-5506. doi: 10.1002/anie.201701220. Epub 2017 Apr 18.
Detailed analysis of the modular Type I polyketide synthase (PKS) involved in the biosynthesis of the marginolactone azalomycin F in mangrove Streptomyces sp. 211726 has shown that only nineteen extension modules are required to accomplish twenty cycles of polyketide chain elongation. Analysis of the products of a PKS mutant specifically inactivated in the dehydratase domain of extension-module 1 showed that this module catalyzes two successive elongations with different outcomes. Strikingly, the enoylreductase domain of this module can apparently be "toggled" off and on : it functions in only the second of these two cycles. This novel mechanism expands our understanding of PKS assembly-line catalysis and may explain examples of apparent non-colinearity in other modular PKS systems.
对参与红树林海洋链霉菌 211726 中产生的马索拉内酯 F 的脂环族内酯模块型 I 聚酮合酶（PKS）的详细分析表明，只有十九个延伸模块就可以完成二十个聚酮链延伸循环。对 PKS 突变体的产物进行分析，该突变体在延伸模块 1 的脱水酶结构域中特异性失活，结果表明该模块催化具有不同结果的两个连续延伸。引人注目的是，该模块的烯酰还原酶结构域显然可以“开启”和“关闭”：它仅在这两个循环中的第二个循环中起作用。这种新机制扩展了我们对 PKS 装配线催化的理解，并可能解释了其他模块化 PKS 系统中明显的非共线性的例子。
Zotero 插件
