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.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mitchell
authors.forename: Noah P
authors.initials: NP
authors.lastname: Dunham
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bergman
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhu
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.forename: Amie K
authors.identifier: 0000-0002-1234-8472
authors.initials: AK
authors.lastname: Boal
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055162:Biocatalysis; D019117:Burkholderia / Q000201:enzymology* / Q000235:genetics; D015870:Gene Expression; D055772:Green Chemistry Technology; D054879:Halogenation; D006219:Halogens / Q000737:chemistry* / Q000378:metabolism; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000737:chemistry / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015202:Protein Engineering; D040681:Structural Homology, Protein; D013379:Substrate Specificity; D019802:Succinic Acid / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D006219:Halogens; D007656:Ketoglutaric Acids; D019802:Succinic Acid; D007501:Iron; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases