Unique electron transfer system of cytochrome P450 monooxygenase includes a mechanism of fatty acid β-oxidation.

ABSTRACT: Cytochrome P450 comprises a group of monooxygenases that hydroxylate xenobiotics and natural compounds with diverse electron transfer systems. Here we identify a natural fusion protein of cytochrome (Cyt) b₅ and Cyt b₅ reductase (CBBR) that transfers electrons from NADH to the cytochrome P450 CYP540A2. This cytochrome P450 system hydroxylates medium-chain fatty acids (MCFAs) to generate (R)-β-hydroxy-MCFAs with 7-12 carbon atoms. Kinetic studies of CYP540A2 mutants indicate that side chains of Ser431 and Gln542 residues bind the carboxyl moiety of MCFAs for hydroxylation at their β-carbons. Pre-steady state kinetics also indicate that a predicted linker region between the FAD- and Cyt b₅-domains of CBBR modulates electron transfer from NADH to CYP540A2. The

SUBMITTER: Kojima S 

PROVIDER: S-EPMC12462446 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature