Requires cobalamin. The enzyme, isolated from the bacterium Streptomyces wedmorensis, is involved in fosfomycin biosynthesis. It is a radical S-adenosyl-L-methionine (SAM) enzyme that contains a [4Fe-4S] center and a methylcob(III)alamin cofactor. The enzyme uses two molecues of SAM for the reaction. One molecule forms a 5'-deoxyadenosyl radical, while the other is used to methylate the cobalamin cofactor. The 5'-deoxyadenosyl radical abstracts a hydrogen from the C2 position of cytidine 5'-{[(2-hydroxyethyl)phosphonoyl]phosphate} forming a free radical that reacts with the methyl group on methylcob(III)alamin at the opposite side from SAM and the [4Fe-4S] cluster with inversion of configuration to produce the (S)-isomer of the methylated product and cob(II)alamin. Both the [4Fe-4S] cluster and the cob(II)alamin need to be reduced by an unknown factor(s) before the enzyme could catalyse another cycle.
Methylcobalamin-Dependent Radical SAM C-Methyltransferase Fom3 Recognizes Cytidylyl-2-hydroxyethylphosphonate and Catalyzes the Nonstereoselective C-Methylation in Fosfomycin Biosynthesis.
Sato S, Kudo F, Kuzuyama T, Hammerschmidt F, Eguchi T.
Title
C-Methylation Catalyzed by Fom3, a Cobalamin-Dependent Radical S-adenosyl-l-methionine Enzyme in Fosfomycin Biosynthesis, Proceeds with Inversion of Configuration.
