基于结构导向的羟化酶重编程以卤化其小分子底物
Structure-Guided Reprogramming of a Hydroxylase To Halogenate Its Small Molecule Substrate.
作者信息
Mitchell Andrew J, Dunham Noah P, Bergman Jonathan A, Wang Bo, Zhu Qin, Chang Wei-Chen, Liu Xinyu, Boal Amie K
机构信息
Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
出版信息
Biochemistry. 2017 Jan 24;56(3):441-444. doi: 10.1021/acs.biochem.6b01173. Epub 2017 Jan 11.
Abstract
Enzymatic installation of chlorine/bromine into unactivated carbon centers provides a versatile, selective, and environmentally friendly alternative to chemical halogenation. Iron(II) and 2-(oxo)-glutarate (Fe/2OG)-dependent halogenases are powerful biocatalysts that are capable of cleaving aliphatic C-H bonds to introduce useful functional groups, including halogens. Using the structure of the Fe/2OG halogenase, WelO5, in complex with its small molecule substrate, we identified a similar N-acyl amino acid hydroxylase, SadA, and reprogrammed it to halogenate its substrate, thereby generating a new chiral haloalkyl center. The work highlights the potential of Fe/2OG enzymes as platforms for development of novel stereospecific catalysts for late-stage C-H functionalization.
摘要
通过酶促反应将氯/溴引入未活化的碳中心，为化学卤化提供了一种通用、选择性且环境友好的替代方法。铁（II）和2-（氧代）-戊二酸（Fe/2OG）依赖性卤化酶是强大的生物催化剂，能够裂解脂肪族C-H键以引入包括卤素在内的有用官能团。利用Fe/2OG卤化酶WelO5与其小分子底物形成的复合物的结构，我们鉴定出一种类似的N-酰基氨基酸羟化酶SadA，并对其进行重新编程以卤化其底物，从而产生一个新的手性卤代烷基中心。这项工作突出了Fe/2OG酶作为开发用于后期C-H官能化的新型立体特异性催化剂平台的潜力。
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