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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.

SUBMITTER: Mitchell AJ

PROVIDER: S-EPMC5852377 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Mitchell Andrew J AJ Dunham Noah P NP Bergman Jonathan A JA Wang Bo B Zhu Qin Q Chang Wei-Chen WC Liu Xinyu X Boal Amie K AK

Biochemistry 20170111 3

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<sup>II</sup>/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 s ...[more]

PMID: 28029241

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