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.
MeSH terms
-
Bacterial Proteins / chemistry*
-
Bacterial Proteins / genetics
-
Bacterial Proteins / metabolism
-
Biocatalysis
-
Burkholderia / enzymology*
-
Burkholderia / genetics
-
Gene Expression
-
Green Chemistry Technology
-
Halogenation
-
Halogens / chemistry*
-
Halogens / metabolism
-
Iron / chemistry
-
Iron / metabolism
-
Ketoglutaric Acids / chemistry
-
Ketoglutaric Acids / metabolism
-
Mixed Function Oxygenases / chemistry*
-
Mixed Function Oxygenases / genetics
-
Mixed Function Oxygenases / metabolism
-
Oxidoreductases / chemistry*
-
Oxidoreductases / genetics
-
Oxidoreductases / metabolism
-
Protein Engineering*
-
Structural Homology, Protein
-
Substrate Specificity
-
Succinic Acid / chemistry
-
Succinic Acid / metabolism
Substances
-
Bacterial Proteins
-
Halogens
-
Ketoglutaric Acids
-
Succinic Acid
-
Iron
-
Mixed Function Oxygenases
-
Oxidoreductases