KEGG   ENZYME: 2.1.1.326
Entry
EC 2.1.1.326                Enzyme                                 

Name
N-acetyldemethylphosphinothricin P-methyltransferase;
phpK (gene name);
bcpD (gene name);
P-methylase
Class
Transferases;
Transferring one-carbon groups;
Methyltransferases
Sysname
S-adenosyl-L-methionine:N-acetyldemethylphosphinothricin P-methyltransferase
Reaction(IUBMB)
2 S-adenosyl-L-methionine + N-acetyldemethylphosphinothricin + reduced acceptor = S-adenosyl-L-homocysteine + 5'-deoxyadenosine + L-methionine + N-acetylphosphinothricin + oxidized acceptor
Reaction(KEGG)
(other) R08873 R08875
Substrate
S-adenosyl-L-methionine [CPD:C00019];
N-acetyldemethylphosphinothricin [CPD:C17949];
reduced acceptor [CPD:C00030]
Product
S-adenosyl-L-homocysteine [CPD:C00021];
5'-deoxyadenosine [CPD:C05198];
L-methionine [CPD:C00073];
N-acetylphosphinothricin [CPD:C17952];
oxidized acceptor
Comment
The enzyme was originally characterized from bacteria that produce the tripeptides bialaphos and phosalacine, which inhibit plant and bacterial glutamine synthetases. It is a radical S-adenosyl-L-methionine (SAM) enzyme that contains a [4Fe-4S] center and a methylcob(III)alamin cofactor. According to the proposed mechanism, the reduced iron-sulfur center donates an electron to SAM, resulting in homolytic cleavage of the carbon-sulfur bond to form a 5'-deoxyadenosyl radical that abstracts the hydrogen atom from the P-H bond of the substrate, forming a phosphinate-centered radical. This radical reacts with methylcob(III)alamin to produce the methylated product and cob(II)alamin, which is reduced by an unknown donor to cob(I)alamin. A potential route for restoring the latter back to methylcob(III)alamin is a nucleophilic attack on a second SAM molecule. The enzyme acts in vivo on N-acetyldemethylphosphinothricin-L-alanyl-L-alanine or N-acetyl-demethylphosphinothricin-L-alanyl-L-leucine, the intermediates in the biosynthesis of bialaphos and phosalacine, respectively. This transformation produces the only example of a carbon-phosphorus-carbon linkage known to occur in nature.
History
EC 2.1.1.326 created 2016
Pathway
ec00440  Phosphonate and phosphinate metabolism
ec01110  Biosynthesis of secondary metabolites
Orthology
K12914  P-methyltransferase
Reference
1  [PMID:1624380]
  Authors
Kamigiri K, Hidaka T, Imai S, Murakami T, Seto H
  Title
Studies on the biosynthesis of bialaphos (SF-1293) 12. C-P bond formation mechanism of bialaphos: discovery of a P-methylation enzyme.
  Journal
J Antibiot (Tokyo) 45:781-7 (1992)
DOI:10.7164/antibiotics.45.781
Reference
2  [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
Reference
3  [PMID:21950770]
  Authors
Werner WJ, Allen KD, Hu K, Helms GL, Chen BS, Wang SC
  Title
In vitro phosphinate methylation by PhpK from Kitasatospora phosalacinea.
  Journal
Biochemistry 50:8986-8 (2011)
DOI:10.1021/bi201220r
Reference
4  [PMID:25224746]
  Authors
Allen KD, Wang SC
  Title
Spectroscopic characterization and mechanistic investigation of P-methyl transfer by a radical SAM enzyme from the marine bacterium Shewanella denitrificans OS217.
  Journal
Biochim Biophys Acta 1844:2135-44 (2014)
DOI:10.1016/j.bbapap.2014.09.009
  Sequence
[sdn:Sden_1168]
Reference
5  [PMID:25594737]
  Authors
Hu K, Werner WJ, Allen KD, Wang SC
  Title
Investigation of enzymatic C-P bond formation using multiple quantum HCP nuclear  magnetic resonance spectroscopy.
  Journal
Magn Reson Chem 53:267-72 (2015)
DOI:10.1002/mrc.4190
Other DBs
ExplorEnz - The Enzyme Database: 2.1.1.326
IUBMB Enzyme Nomenclature: 2.1.1.326
ExPASy - ENZYME nomenclature database: 2.1.1.326
BRENDA, the Enzyme Database: 2.1.1.326
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