| EC |
2.1.1.308 |
| 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[(S)-2-hydroxypropyl]phosphonoyl}phosphate) + oxidized acceptor |
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For diagram of fosfomycin biosynthesis, click here |
| 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 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. |
| Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
| References: |
| 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. [DOI] [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. [DOI] [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. [DOI] [PMID: 28678474] |
| 4. |
Blaszczyk, A.J. and Booker, S.J. A (re)discovery of the Fom3 substrate. Biochemistry 57 (2018) 891–892. [DOI] [PMID: 29345912] |
| 5. |
Sato, S., Kudo, F., Kuzuyama, T., Hammerschmidt, F. and Eguchi, T. C-methylation catalyzed by Fom3, a cobalamin-dependent radical S-adenosyl-L-methionine enzyme in fosfomycin biosynthesis, proceeds with inversion of configuration. Biochemistry 57 (2018) 4963–4966. [DOI] [PMID: 29966085] |
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| [EC 2.1.1.308 created 2014, modified 2019] |
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