Selective <i>α</i>-Hydroxyketone Formation and Subsequent C-C Bond Cleavage by Cytochrome P450 Monooxygenase Enzymes.

ABSTRACT: The heme enzymes of the cytochrome P450 superfamily (CYPs) catalyze oxidation reactions with a high level of selectivity. Here, the CYP199A4 enzyme from the bacterium Rhodopseudomonas palustris HaA2 is used to catalyze the hydroxylation of carbonyl-containing compounds to generate α-hydroxyketones. Both 4-propionyl- and 4-(2-oxopropyl)-benzoic acids were regioselectively hydroxylated by this enzyme to generate α-hydroxyketone metabolites, 4-(2-hydroxypropanoyl)benzoic acid and 4-(1-hydroxy-2-oxopropyl)benzoic acid, respectively, with high stereoselectivity. Co-crystallization of CYP199A4 with each substrate allowed high-resolution X-ray crystal structures of the enzyme bound with both to be determined. These provide a rationale for biochemical observations related to s

SUBMITTER: Lee JHZ 

PROVIDER: S-EPMC11793330 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature