MilM from mildiomycin biosynthesis is an oxygen-, pyridoxal phosphate-dependent arginine hydroxylase.

ABSTRACT: Mildiomycin, a potent antifungal, is biosynthesized through a complex pathway involving the enzyme MilM. This study reassigns MilM as an oxygen (O₂)-, pyridoxal phosphate-dependent hydroxylase that hydroxylates the l-arginine-derived side chain of mildiomycin at the C4 position. This activity is conserved with the homologs MppP from enduracididine biosynthesis and RohP from azomycin biosynthesis. We found MilM effectively hydroxylates ʟ-arginine via both a two- and four-electron oxidation pathway in a O₂-dependent manner. We also show the hydroxyl group originates from H₂O, and the reaction mechanism transitions through conjugated quinonoid intermediates. The O₂-, pyridoxal phosphate-dependent transformation of l-arginine catalyzed by MilM ultima

SUBMITTER: Edwards KEK 

PROVIDER: S-EPMC12464687 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature