Enzyme engineering of cytochrome P450 RosC provides mechanistic insights into factors controlling iterative oxidation.

ABSTRACT: Cytochrome P450 enzymes capable of performing iterative oxidation at the same substrate site contribute to compound diversification; however, reaction control is also necessary for the efficient production of the desired compound. RosC, a cytochrome P450 enzyme involved in the biosynthesis of the 16-membered ring macrolide antibiotic rosamicin, catalyzes stepwise oxidation of the ethyl group at C-20 via hydroxylation to an alcohol, followed by successive oxidation to the corresponding aldehyde and carboxylic acid. The P107S/L176Q mutant produces the hydroxylated intermediate in the first oxidation step, but the efficiency of the subsequent conversion to aldehyde and carboxylic acid is significantly reduced. To elucidate the factors responsible for the reduced efficiency of the second and s

SUBMITTER: Iizaka Y 

PROVIDER: S-EPMC12696090 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature