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 (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 functional

SUBMITTER: Mitchell AJ 

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

REPOSITORIES: biostudies-literature