Accepted name: cytidylyl-2-hydroxyethylphosphonate methyltransferase
Reaction: 2 S-adenosyl-L-methionine + cytidine 5′-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} + reduced acceptor = S-adenosyl-L-homocysteine + 5′-deoxyadenosine + L-methionine + cytidine 5′-{[hydroxy(2-hydroxypropyl)phosphonoyl]phosphate} + oxidized acceptor
Other name(s): Fom3; S-adenosyl-L-methionine:methylcob(III)alamin:2-hydroxyethylphosphonate methyltransferase (incorrect); 2-hydroxyethylphosphonate methyltransferase (incorrect)
Systematic name: S-adenosyl-L-methionine:cytidine 5′-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} C-methyltransferase
Comments: 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 to produce a racemic mix of methylated products 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.
1.  Woodyer, R.D., Li, G., Zhao, H. and van der Donk, W.A. New insight into the mechanism of methyl transfer during the biosynthesis of fosfomycin. Chem. Commun. (Camb.) (2007) 359–361. [PMID: 17220970]
2.  Allen, K.D. and Wang, S.C. Initial characterization of Fom3 from Streptomyces wedmorensis: The methyltransferase in fosfomycin biosynthesis. Arch. Biochem. Biophys. 543 (2014) 67–73. [PMID: 24370735]
3.  Sato, S., Kudo, F., Kim, S.Y., Kuzuyama, T. and Eguchi, T. Methylcobalamin-dependent radical SAM C-methyltransferase Fom3 recognizes cytidylyl-2-hydroxyethylphosphonate and catalyzes the nonstereoselective C-methylation in fosfomycin biosynthesis. Biochemistry 56 (2017) 3519–3522. [PMID: 28678474]
4.  Blaszczyk, A.J. and Booker, S.J. A (re)discovery of the Fom3 substrate. Biochemistry 57 (2018) 891–892. [PMID: 29345912]
[EC created 2014, modified 2019]