KEGG   ORTHOLOGY: K12903
Entry
K12903            Tight     KO                                     
Symbol
fom4
Name
(S)-2-hydroxypropylphosphonic acid epoxidase [EC:1.11.1.23]
Pathway
map00998  Biosynthesis of various antibiotics
map01100  Metabolic pathways
map01110  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 antibiotics
    K12903  fom4; (S)-2-hydroxypropylphosphonic acid epoxidase
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.11  Acting on a peroxide as acceptor
   1.11.1  Peroxidases
    1.11.1.23  (S)-2-hydroxypropylphosphonic acid epoxidase
     K12903  fom4; (S)-2-hydroxypropylphosphonic acid epoxidase
Other DBs
RN: R08863
Genes
AG: BAA32491(fom4)
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
PMID:7500951
  Authors
Hidaka T, Goda M, Kuzuyama T, Takei N, Hidaka M, Seto H
  Title
Cloning and nucleotide sequence of fosfomycin biosynthetic genes of Streptomyces wedmorensis.
  Journal
Mol Gen Genet 249:274-80 (1995)
DOI:10.1007/BF00290527
  Sequence
LinkDB

KEGG   ORTHOLOGY: K22392
Entry
K22392            Tight     KO                                     
Symbol
hppE
Name
(S)-2-hydroxypropylphosphonic acid epoxidase [EC:1.11.1.23]
Pathway
map00998  Biosynthesis of various antibiotics
map01100  Metabolic pathways
map01110  Biosynthesis of secondary metabolites
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09110 Biosynthesis of other secondary metabolites
   00998 Biosynthesis of various antibiotics
    K22392  hppE; (S)-2-hydroxypropylphosphonic acid epoxidase
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.11  Acting on a peroxide as acceptor
   1.11.1  Peroxidases
    1.11.1.23  (S)-2-hydroxypropylphosphonic acid epoxidase
     K22392  hppE; (S)-2-hydroxypropylphosphonic acid epoxidase
Other DBs
RN: R08863
Genes
AG: BAA94418(hppE)
Reference
  Authors
Munos JW, Moon SJ, Mansoorabadi SO, Chang W, Hong L, Yan F, Liu A, Liu HW
  Title
Purification and characterization of the epoxidase catalyzing the formation of fosfomycin from Pseudomonas syringae.
  Journal
Biochemistry 47:8726-35 (2008)
DOI:10.1021/bi800877v
  Sequence
LinkDB

KEGG   ENZYME: 1.11.1.23
Entry
EC 1.11.1.23                Enzyme                                 
Name
(S)-2-hydroxypropylphosphonic acid epoxidase;
HPP epoxidase;
HppE;
2-hydroxypropylphosphonic acid epoxidase;
Fom4;
(S)-2-hydroxypropylphosphonate epoxidase
Class
Oxidoreductases;
Acting on a peroxide as acceptor;
Peroxidases
Sysname
(S)-2-hydroxypropylphosphonate:hydrogen-peroxide epoxidase
Reaction(IUBMB)
(S)-2-hydroxypropylphosphonate + H2O2 = (1R,2S)-1,2-epoxypropylphosphonate + 2 H2O [RN:R08863]
Reaction(KEGG)
R08863
Substrate
(S)-2-hydroxypropylphosphonate [CPD:C06452];
H2O2 [CPD:C00027]
Product
(1R,2S)-1,2-epoxypropylphosphonate;
H2O [CPD:C00001]
Comment
This is the last enzyme in the biosynthetic pathway of fosfomycin, a broad-spectrum antibiotic produced by certain Streptomyces species. Contains non heme iron that forms a iron(IV)-oxo (ferryl) complex with hydrogen peroxide, which functions as a proton abstractor from the substrate [7].
History
EC 1.11.1.23 created 2011 as EC 1.14.19.7, transferred 2014 to EC 1.11.1.23
Pathway
ec00998  Biosynthesis of various antibiotics
ec01100  Metabolic pathways
ec01110  Biosynthesis of secondary metabolites
Orthology
K12903  (S)-2-hydroxypropylphosphonic acid epoxidase
K22392  (S)-2-hydroxypropylphosphonic acid epoxidase
Reference
1  [PMID:18656958]
  Authors
Munos JW, Moon SJ, Mansoorabadi SO, Chang W, Hong L, Yan F, Liu A, Liu HW
  Title
Purification and characterization of the epoxidase catalyzing the formation of fosfomycin from Pseudomonas syringae.
  Journal
Biochemistry 47:8726-35 (2008)
DOI:10.1021/bi800877v
  Sequence
Reference
2  [PMID:17927218]
  Authors
Yan F, Moon SJ, Liu P, Zhao Z, Lipscomb JD, Liu A, Liu HW
  Title
Determination of the substrate binding mode to the active site iron of (S)-2-hydroxypropylphosphonic acid epoxidase using 17O-enriched substrates and substrate analogues.
  Journal
Biochemistry 46:12628-38 (2007)
DOI:10.1021/bi701370e
Reference
3  [PMID:7500951]
  Authors
Hidaka T, Goda M, Kuzuyama T, Takei N, Hidaka M, Seto H
  Title
Cloning and nucleotide sequence of fosfomycin biosynthetic genes of Streptomyces wedmorensis.
  Journal
Mol Gen Genet 249:274-80 (1995)
DOI:10.1007/BF00290527
  Sequence
Reference
4  [PMID:15315444]
  Authors
Liu P, Mehn MP, Yan F, Zhao Z, Que L Jr, Liu HW
  Title
Oxygenase activity in the self-hydroxylation of (s)-2-hydroxypropylphosphonic acid epoxidase involved in fosfomycin biosynthesis.
  Journal
J Am Chem Soc 126:10306-12 (2004)
DOI:10.1021/ja0475050
Reference
5  [PMID:16015285]
  Authors
Higgins LJ, Yan F, Liu P, Liu HW, Drennan CL
  Title
Structural insight into antibiotic fosfomycin biosynthesis by a mononuclear iron  enzyme.
  Journal
Nature 437:838-44 (2005)
DOI:10.1038/nature03924
  Sequence
Reference
6  [PMID:16511089]
  Authors
Cameron S, McLuskey K, Chamberlayne R, Hallyburton I, Hunter WN
  Title
Initiating a crystallographic analysis of recombinant (S)-2-hydroxypropylphosphonic acid epoxidase from Streptomyces wedmorensis.
  Journal
Acta Crystallogr Sect F Struct Biol Cryst Commun 61:534-6 (2005)
DOI:10.1107/S1744309105012376
Reference
7  [PMID:24114783]
  Authors
Wang C, Chang WC, Guo Y, Huang H, Peck SC, Pandelia ME, Lin GM, Liu HW, Krebs C, Bollinger JM Jr
  Title
Evidence that the fosfomycin-producing epoxidase, HppE, is a non-heme-iron peroxidase.
  Journal
Science 342:991-5 (2013)
DOI:10.1126/science.1240373
Other DBs
ExplorEnz - The Enzyme Database: 1.11.1.23
IUBMB Enzyme Nomenclature: 1.11.1.23
ExPASy - ENZYME nomenclature database: 1.11.1.23
BRENDA, the Enzyme Database: 1.11.1.23
LinkDB

KEGG   REACTION: R08863
Entry
R08863                      Reaction                               
Name
(S)-2-hydroxypropylphosphonate,NADH:oxygen epoxidase
Definition
(S)-2-Hydroxypropylphosphonate + Hydrogen peroxide <=> Fosfomycin + 2 H2O
Equation
Reaction class
RC01298  C06452_C06454
Enzyme
Pathway
rn00998  Biosynthesis of various antibiotics
rn01100  Metabolic pathways
rn01110  Biosynthesis of secondary metabolites
Module
M00903  Fosfomycin biosynthesis, phosphoenolpyruvate => fosfomycin
Orthology
K12903  (S)-2-hydroxypropylphosphonic acid epoxidase [EC:1.11.1.23]
K22392  (S)-2-hydroxypropylphosphonic acid epoxidase [EC:1.11.1.23]
Other DBs
RHEA: 10811
LinkDB

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