KEGG   ORTHOLOGY: K12902
Entry
K12902            Tight     KO                                     

Name
fom3
Definition
phosphonoacetaldehyde methylase [EC:2.1.1.308]
Pathway
ko00998  Biosynthesis of various secondary metabolites - part 2
ko01100  Metabolic pathways
ko01110  Biosynthesis of secondary metabolites
Module
M00903  Fosfomycin biosynthesis, phosphoenolpyruvate => fosfomycin
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09110 Biosynthesis of other secondary metabolites
   00998 Biosynthesis of various secondary metabolites - part 2
    K12902  fom3; phosphonoacetaldehyde methylase
Enzymes [BR:ko01000]
 2. Transferases
  2.1  Transferring one-carbon groups
   2.1.1  Methyltransferases
    2.1.1.308  cytidylyl-2-hydroxyethylphosphonate methyltransferase
     K12902  fom3; phosphonoacetaldehyde methylase
Other DBs
RN: R08862 R12497
Genes
AG: ACG70826(fom3) BAA32490(fom3)
Reference
PMID:7789803
  Authors
Hidaka T, Hidaka M, Kuzuyama T, Seto H
  Title
Sequence of a P-methyltransferase-encoding gene isolated from a bialaphos-producing Streptomyces hygroscopicus.
  Journal
Gene 158:149-50 (1995)
DOI:10.1016/0378-1119(95)00101-B
  Sequence
Reference
  Authors
Metcalf WW, van der Donk WA
  Title
Biosynthesis of phosphonic and phosphinic acid natural products.
  Journal
Annu Rev Biochem 78:65-94 (2009)
DOI:10.1146/annurev.biochem.78.091707.100215
Reference
  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

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(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(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 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.
History
EC 2.1.1.308 created 2014, modified 2019
Pathway
ec00998  Biosynthesis of various secondary metabolites - part 2
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
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

KEGG   REACTION: R12497
Entry
R12497                      Reaction                               

Name
S-adenosyl-L-methionine:cytidine 5'-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} C-methyltransferase
Definition
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} + Acceptor
Equation
Reaction class
RC02370  C22216_C22217
Enzyme
Pathway
rn00998  Biosynthesis of various secondary metabolites - part 2
rn01100  Metabolic pathways
rn01110  Biosynthesis of secondary metabolites
Module
M00903  Fosfomycin biosynthesis, phosphoenolpyruvate => fosfomycin
Orthology
K12902  phosphonoacetaldehyde methylase [EC:2.1.1.308]

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