KEGG   ENZYME: 2.1.1.308
Entry
EC 2.1.1.308                Enzyme                                 
Name
cytidylyl-2-hydroxyethylphosphonate methyltransferase;
Fom3;
S-adenosyl-L-methionine:methylcob(III)alamin:2-hydroxyethylphosphonate methyltransferase (incorrect);
2-hydroxyethylphosphonate methyltransferase (incorrect)
Class
Transferases;
Transferring one-carbon groups;
Methyltransferases
Sysname
S-adenosyl-L-methionine:cytidine 5'-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} C-methyltransferase
Reaction(IUBMB)
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 [RN:R12497]
Reaction(KEGG)
R12497;
(other) R08862
Substrate
S-adenosyl-L-methionine [CPD:C00019];
cytidine 5'-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} [CPD:C22216];
reduced acceptor [CPD:C00030]
Product
S-adenosyl-L-homocysteine [CPD:C00021];
5'-deoxyadenosine [CPD:C05198];
L-methionine [CPD:C00073];
cytidine 5'-({hydroxy[(S)-2-hydroxypropyl]phosphonoyl}phosphate) [CPD:C22217];
oxidized acceptor
Comment
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.
History
EC 2.1.1.308 created 2014, modified 2019
Pathway
ec00998  Biosynthesis of various antibiotics
ec01100  Metabolic pathways
ec01110  Biosynthesis of secondary metabolites
Orthology
K12902  phosphonoacetaldehyde methylase
Reference
1  [PMID:17220970]
  Authors
Woodyer RD, Li G, Zhao H, van der Donk WA
  Title
New insight into the mechanism of methyl transfer during the biosynthesis of fosfomycin.
  Journal
Chem Commun (Camb) 359-61 (2007)
DOI:10.1039/b614678c
  Sequence
Reference
2  [PMID:24370735]
  Authors
Allen KD, Wang SC
  Title
Initial characterization of Fom3 from Streptomyces wedmorensis: The methyltransferase in fosfomycin biosynthesis.
  Journal
Arch Biochem Biophys 543:67-73 (2014)
DOI:10.1016/j.abb.2013.12.004
  Sequence
Reference
3  [PMID:28678474]
  Authors
Sato S, Kudo F, Kim SY, Kuzuyama T, Eguchi T
  Title
Methylcobalamin-Dependent Radical SAM C-Methyltransferase Fom3 Recognizes Cytidylyl-2-hydroxyethylphosphonate and Catalyzes the Nonstereoselective C-Methylation in Fosfomycin Biosynthesis.
  Journal
Biochemistry 56:3519-3522 (2017)
DOI:10.1021/acs.biochem.7b00472
Reference
4  [PMID:29345912]
  Authors
Blaszczyk AJ, Booker SJ
  Title
A (Re)Discovery of the Fom3 Substrate.
  Journal
Biochemistry 57:891-892 (2018)
DOI:10.1021/acs.biochem.7b01281
Reference
5  [PMID:29966085]
  Authors
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.
  Journal
Biochemistry 57:4963-4966 (2018)
DOI:10.1021/acs.biochem.8b00614
Other DBs
ExplorEnz - The Enzyme Database: 2.1.1.308
IUBMB Enzyme Nomenclature: 2.1.1.308
ExPASy - ENZYME nomenclature database: 2.1.1.308
BRENDA, the Enzyme Database: 2.1.1.308

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