@article {Edwards2025-jw,
	title = {{MilM} from mildiomycin biosynthesis is an oxygen-, pyridoxal phosphate-dependent arginine hydroxylase},
	journal = {J. Biol. Chem.},
	number = {110605},
	year = {2025},
	pages = {110605},
	publisher = {Elsevier BV},
	abstract = {Mildiomycin, a potent antifungal, is biosynthesized through a complex pathway involving the enzyme MilM. This study reassigns MilM as an 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 L-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 ultimately yields the 5-guanidino-2,4-dihydroxyvalerate side chain of mildiomycin. Re-characterization of this essential step in mildiomycin helps elucidate the full pathway of mildiomycin production.},
	author = {Edwards, Kairel E K and Wolf, Megan E and Eltis, Lindsay D and Ryan, Katherine S}
}
