Structure-Guided Reprogramming of a Hydroxylase To Halogenate Its Small Molecule Substrate
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- 作者：Andrew J. Mitchell ; Noah P. Dunham ; Jonathan A. Bergman ; Bo Wang ; Qin Zhu ; Wei-chen Chang ; Xinyu Liu ; Amie K. Boal
- 刊名：Biochemistry
- 出版年：2017
- 出版时间：January 24, 2017
- 年：2017
- 卷：56
- 期：3
- 页码：441-444
- 全文大小：301K
- ISSN：1520-4995
文摘
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 (FeII/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 FeII/2OG enzymes as platforms for development of novel stereospecific catalysts for late-stage C–H functionalization.