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 journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)441-444
Number of pages4
Issue number3
StatePublished - Jan 24 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry


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