A fungal ketoreductase domain that displays substrate-dependent stereospecificity.

A fungal ketoreductase domain that displays substrate-dependent stereospecificity.
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DOI:
10.1038/nchembio.912
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发表时间:
2012-03-11
影响因子:
14.8
通讯作者:
Tang, Yi
Tang, Yi
中科院分区:
生物学1区
文献类型:
--
作者:
Zhou, Hui;Gao, Zhizeng;Qiao, Kangjian;Wang, Jingjing;Vederas, John C.;Tang, Yi

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丝状真菌的重复高还原聚酮酶(HR-PKS)是迄今为止发现的最复杂和最神秘的PKS类型。在这里,我们发现了一个不寻常的编程水平的hypothemycin HR-PKS,其中一个单一的酮还原酶结构域显示立体特异性,是由底物长度控制。负责这一功能的结构域的映射允许的天然产物脱氢玉米赤霉烯醇的非天然非对映异构体的生物合成。
Iterative highly-reducing polyketide synthases (HR-PKSs) from filamentous fungi are the most complex and enigmatic type of PKS discovered to date. Here we uncover an unusual level of programming by the hypothemycin HR-PKS, in which a single ketoreductase domain displays stereospecificity that is controlled by substrate length. Mapping of the structural domains responsible for this feature allowed the biosynthesis of an unnatural diastereomer of the natural product dehydrozearalenol.
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