Structure-Guided Reprogramming of a Hydroxylase to Halogenate Its Small Molecule Substrate

Andrew J. Mitchell; Noah P. Dunham; Jonathan A. Bergman; Bo Wang; Qin Zhu; Wei Chen Chang; Xinyu Liu; Amie K. Boal

doi:10.1021/acs.biochem.6b01173

Structure-Guided Reprogramming of a Hydroxylase to Halogenate Its Small Molecule Substrate

Andrew J. Mitchell, Noah P. Dunham, Jonathan A. Bergman, Bo Wang, Qin Zhu, Wei Chen Chang, Xinyu Liu, Amie K. Boal

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

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^II/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^II/2OG enzymes as platforms for development of novel stereospecific catalysts for late-stage C-H functionalization.

Original language	English (US)
Pages (from-to)	441-444
Number of pages	4
Journal	Biochemistry
Volume	56
Issue number	3
DOIs	https://doi.org/10.1021/acs.biochem.6b01173
State	Published - Jan 24 2017

All Science Journal Classification (ASJC) codes

Biochemistry

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10.1021/acs.biochem.6b01173

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title = "Structure-Guided Reprogramming of a Hydroxylase to Halogenate Its Small Molecule Substrate",

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 (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.",

author = "Mitchell, {Andrew J.} and Dunham, {Noah P.} and Bergman, {Jonathan A.} and Bo Wang and Qin Zhu and Chang, {Wei Chen} and Xinyu Liu and Boal, {Amie K.}",

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T1 - Structure-Guided Reprogramming of a Hydroxylase to Halogenate Its Small Molecule Substrate

AU - Mitchell, Andrew J.

AU - Dunham, Noah P.

AU - Bergman, Jonathan A.

AU - Wang, Bo

AU - Zhu, Qin

AU - Chang, Wei Chen

AU - Liu, Xinyu

AU - Boal, Amie K.

PY - 2017/1/24

Y1 - 2017/1/24

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AB - 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.

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Structure-Guided Reprogramming of a Hydroxylase to Halogenate Its Small Molecule Substrate

Abstract

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