KEGG ORTHOLOGY: K12903

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

Reaction

R08863

(S)-2-hydroxypropylphosphonate,NADH:oxygen epoxidase

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

Genes

AG:	BAA32491(fom4)

Reference

PMID:19489722

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

[ag:BAA32491]

LinkDB

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

Reaction

R08863

(S)-2-hydroxypropylphosphonate,NADH:oxygen epoxidase

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

Genes

AG:	BAA94418(hppE)

Reference

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

[ag:BAA94418]

LinkDB

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

[ag:BAA94418]

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

[ag:BAA32491]

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

[ag:BAA32491]

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

REACTION: R08863

Entry

R08863                      Reaction

Name

(S)-2-hydroxypropylphosphonate,NADH:oxygen epoxidase

Definition

(S)-2-Hydroxypropylphosphonate + Hydrogen peroxide <=> Fosfomycin + 2 H2O

Equation

C06452 + C00027 <=> C06454 + 2 C00001

Reaction class

RC01298

C06452_C06454

Enzyme

1.11.1.23

Pathway

rn00998

Biosynthesis of various antibiotics

rn01100

Metabolic pathways

rn01110

Biosynthesis of secondary metabolites

Module

M00903

Fosfomycin biosynthesis, phosphoenolpyruvate => fosfomycin

Brite

Enzymatic reactions [BR:br08201]
1. Oxidoreductase reactions
  1.11  Acting on a peroxide as acceptor
   1.11.1  Peroxidases
    1.11.1.23
     R08863  (S)-2-Hydroxypropylphosphonate + Hydrogen peroxide <=> Fosfomycin + 2 H2O

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

DBGET integrated database retrieval system