Biosynthesis of reveromycin derivatives by altering the regioselectivity of cytochrome P450revI.

ABSTRACT: Reveromycin A (RM-A) (1) has a 6,6-spiroacetal core structure that is important for its biological activity. However, 1 undergoes a spiroacetal rearrangement to form RM-B (2) with a 5,6-spiroacetal core, which exhibits reduced bioactivity. This undesired rearrangement is partly due to the hemisuccinate moiety at the C18 position of 1. In 1 biosynthesis, P450revI catalyses the C18-hydroxylation of RM-T (3), which is essential for its subsequent hemisuccinylation to generate 1. In this study, we aimed to alter the P450revI regioselectivity to improve the stability of the 6,6-spiroacetal core and expand the structural diversity of RMs. Candidate amino acid residues for mutagenesis studies were selected by comparing the co-crystal structure of P450revI with the docking models of the P450revI m

SUBMITTER: Yong YF 

PROVIDER: S-EPMC12183568 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature