ID   FOM1_STRWE              Reviewed;         435 AA.
AC   P96074;
DT   10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   02-SEP-2026, entry version 100.
DE   RecName: Full=Fosfomycin biosynthesis bifunctional protein Fom1 {ECO:0000305};
DE   Includes:
DE     RecName: Full=2-hydroxyethylphosphonate cytidylyltransferase {ECO:0000305};
DE              EC=2.7.7.104 {ECO:0000269|PubMed:28727444};
DE   Includes:
DE     RecName: Full=Phosphoenolpyruvate phosphomutase {ECO:0000303|PubMed:28727444};
DE              Short=PEP mutase {ECO:0000305};
DE              Short=PEP phosphomutase {ECO:0000303|PubMed:28727444};
DE              EC=5.4.2.9 {ECO:0000269|PubMed:28727444};
GN   Name=fom1 {ECO:0000303|PubMed:7500951};
OS   Streptomyces wedmorensis.
OC   Bacteria; Bacillati; Actinomycetota; Actinomycetes; Kitasatosporales;
OC   Streptomycetaceae; Streptomyces.
OX   NCBI_TaxID=43759;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PATHWAY.
RC   STRAIN=144-91;
RX   PubMed=7500951; DOI=10.1007/bf00290527;
RA   Hidaka T., Goda M., Kuzuyama T., Takei N., Hidaka M., Seto H.;
RT   "Cloning and nucleotide sequence of fosfomycin biosynthetic genes of
RT   Streptomyces wedmorensis.";
RL   Mol. Gen. Genet. 249:274-280(1995).
RN   [2] {ECO:0007744|PDB:5X3D}
RP   X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 1-139 IN COMPLEX WITH HEP-CMP,
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY, DOMAIN, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=28727444; DOI=10.1021/acschembio.7b00419;
RA   Cho S.H., Kim S.Y., Tomita T., Shiraishi T., Park J.S., Sato S., Kudo F.,
RA   Eguchi T., Funa N., Nishiyama M., Kuzuyama T.;
RT   "Fosfomycin biosynthesis via transient cytidylylation of 2-
RT   hydroxyethylphosphonate by the bifunctional Fom1 enzyme.";
RL   ACS Chem. Biol. 12:2209-2215(2017).
CC   -!- FUNCTION: Bifunctional enzyme that catalyzes two steps during
CC       fosfomycin biosynthesis (PubMed:28727444). It catalyzes the conversion
CC       of phosphoenolpyruvate (PEP) to phosphonopyruvate (PnPy), the first
CC       step of the pathway. It also catalyzes the cytidylylation of the 2-
CC       hydroxyethylphosphonate (HEP) intermediate to produce cytidylyl-2-
CC       hydroxyethylphosphonate (HEP-CMP), the fourth step of the pathway
CC       (PubMed:28727444). {ECO:0000269|PubMed:28727444}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-hydroxyethylphosphonate + CTP = cytidine 5'-{[hydroxy(2-
CC         hydroxyethyl)phosphonoyl]phosphate} + diphosphate;
CC         Xref=Rhea:RHEA:63420, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563,
CC         ChEBI:CHEBI:60991, ChEBI:CHEBI:142876; EC=2.7.7.104;
CC         Evidence={ECO:0000269|PubMed:28727444};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63421;
CC         Evidence={ECO:0000269|PubMed:28727444};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=phosphoenolpyruvate + H(+) = 3-phosphonopyruvate;
CC         Xref=Rhea:RHEA:17013, ChEBI:CHEBI:15378, ChEBI:CHEBI:58702,
CC         ChEBI:CHEBI:71402; EC=5.4.2.9;
CC         Evidence={ECO:0000269|PubMed:28727444};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17014;
CC         Evidence={ECO:0000269|PubMed:28727444};
CC   -!- COFACTOR:
CC       Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC         Evidence={ECO:0000269|PubMed:28727444};
CC       Note=The CyTase reaction requires a divalent metal ion. Highest
CC       activity is observed with Co(2+), but it can also use Mg2(+), Ni2(+),
CC       Fe2(+) or Mn2(+). {ECO:0000269|PubMed:28727444};
CC   -!- PATHWAY: Antibiotic biosynthesis; fosfomycin biosynthesis.
CC       {ECO:0000269|PubMed:28727444}.
CC   -!- DOMAIN: Contains an N-terminal cytidylyltransferase (CyTase) domain and
CC       a C-terminal phosphoenolpyruvate phosphomutase domain.
CC       {ECO:0000269|PubMed:28727444}.
CC   -!- DISRUPTION PHENOTYPE: Deletion mutant does not produce fosfomycin.
CC       {ECO:0000269|PubMed:28727444}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the
CC       cytidylyltransferase family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the isocitrate
CC       lyase/PEP mutase superfamily. PEP mutase family. {ECO:0000305}.
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DR   EMBL; AB016934; BAA32495.1; -; Genomic_DNA.
DR   PIR; S60206; S60206.
DR   RefSeq; WP_017236167.1; NZ_JBIRVY010000005.1.
DR   PDB; 5X3D; X-ray; 1.93 A; A=1-139.
DR   AlphaFoldDB; P96074; -.
DR   SMR; P96074; -.
DR   KEGG; ag:BAA32495; -.
DR   BioCyc; MetaCyc:MONOMER-13657; -.
DR   UniPathway; UPA01071; -.
DR   GO; GO:0050188; F:phosphoenolpyruvate mutase activity; EXP:UniProtKB.
DR   CDD; cd02170; cytidylyltransferase; 1.
DR   CDD; cd00377; ICL_PEPM; 1.
DR   Gene3D; 3.40.50.620; HUPs; 1.
DR   Gene3D; 3.20.20.60; Phosphoenolpyruvate-binding domains; 1.
DR   InterPro; IPR050385; Archaeal_FAD_synthase.
DR   InterPro; IPR004821; Cyt_trans-like.
DR   InterPro; IPR039556; ICL/PEPM.
DR   InterPro; IPR012698; PEnolPyrv_PMutase_core.
DR   InterPro; IPR015813; Pyrv/PenolPyrv_kinase-like_dom.
DR   InterPro; IPR040442; Pyrv_kinase-like_dom_sf.
DR   InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR   NCBIfam; TIGR00125; cyt_tran_rel; 1.
DR   NCBIfam; TIGR02320; PEP_mutase; 1.
DR   PANTHER; PTHR43793; FAD SYNTHASE; 1.
DR   PANTHER; PTHR43793:SF1; FAD SYNTHASE; 1.
DR   Pfam; PF01467; CTP_transf_like; 1.
DR   Pfam; PF13714; PEP_mutase; 1.
DR   SUPFAM; SSF52374; Nucleotidylyl transferase; 1.
DR   SUPFAM; SSF51621; Phosphoenolpyruvate/pyruvate domain; 1.
DR   PDBsum; 5X3D; -.
PE   1: Evidence at protein level;
KW   3D-structure; Antibiotic biosynthesis; Cobalt; Isomerase;
KW   Multifunctional enzyme; Nucleotidyltransferase; Pyruvate; Transferase.
FT   CHAIN           1..435
FT                   /note="Fosfomycin biosynthesis bifunctional protein Fom1"
FT                   /id="PRO_0000452003"
FT   REGION          1..139
FT                   /note="Cytidylyltransferase"
FT                   /evidence="ECO:0000305|PubMed:28727444"
FT   REGION          140..435
FT                   /note="Phosphoenolpyruvate phosphomutase"
FT                   /evidence="ECO:0000305|PubMed:28727444"
FT   ACT_SITE        206
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q84G06"
FT   BINDING         11..12
FT                   /ligand="cytidine 5'-{[hydroxy(2-
FT                   hydroxyethyl)phosphonoyl]phosphate}"
FT                   /ligand_id="ChEBI:CHEBI:142876"
FT                   /evidence="ECO:0000269|PubMed:28727444"
FT   BINDING         45..46
FT                   /ligand="cytidine 5'-{[hydroxy(2-
FT                   hydroxyethyl)phosphonoyl]phosphate}"
FT                   /ligand_id="ChEBI:CHEBI:142876"
FT                   /evidence="ECO:0000269|PubMed:28727444"
FT   BINDING         77
FT                   /ligand="cytidine 5'-{[hydroxy(2-
FT                   hydroxyethyl)phosphonoyl]phosphate}"
FT                   /ligand_id="ChEBI:CHEBI:142876"
FT                   /evidence="ECO:0000269|PubMed:28727444"
FT   BINDING         91..94
FT                   /ligand="cytidine 5'-{[hydroxy(2-
FT                   hydroxyethyl)phosphonoyl]phosphate}"
FT                   /ligand_id="ChEBI:CHEBI:142876"
FT                   /evidence="ECO:0000269|PubMed:28727444"
FT   BINDING         100
FT                   /ligand="cytidine 5'-{[hydroxy(2-
FT                   hydroxyethyl)phosphonoyl]phosphate}"
FT                   /ligand_id="ChEBI:CHEBI:142876"
FT                   /evidence="ECO:0000269|PubMed:28727444"
FT   BINDING         124..127
FT                   /ligand="cytidine 5'-{[hydroxy(2-
FT                   hydroxyethyl)phosphonoyl]phosphate}"
FT                   /ligand_id="ChEBI:CHEBI:142876"
FT                   /evidence="ECO:0000269|PubMed:28727444"
FT   STRAND          5..10
FT                   /evidence="ECO:0007829|PDB:5X3D"
FT   HELIX           17..29
FT                   /evidence="ECO:0007829|PDB:5X3D"
FT   STRAND          30..37
FT                   /evidence="ECO:0007829|PDB:5X3D"
FT   HELIX           39..43
FT                   /evidence="ECO:0007829|PDB:5X3D"
FT   HELIX           47..49
FT                   /evidence="ECO:0007829|PDB:5X3D"
FT   HELIX           53..60
FT                   /evidence="ECO:0007829|PDB:5X3D"
FT   STRAND          66..72
FT                   /evidence="ECO:0007829|PDB:5X3D"
FT   HELIX           78..84
FT                   /evidence="ECO:0007829|PDB:5X3D"
FT   STRAND          87..92
FT                   /evidence="ECO:0007829|PDB:5X3D"
FT   HELIX           93..96
FT                   /evidence="ECO:0007829|PDB:5X3D"
FT   HELIX           101..112
FT                   /evidence="ECO:0007829|PDB:5X3D"
FT   TURN            113..115
FT                   /evidence="ECO:0007829|PDB:5X3D"
FT   STRAND          117..121
FT                   /evidence="ECO:0007829|PDB:5X3D"
SQ   SEQUENCE   435 AA;  48290 MW;  458EC236BCACACD9 CRC64;
     MQRPIVYVGM SADLIHPGHI NILSRAAELG DITIGLLTDA AIASYKRLPH MTYEQRKAVV
     ENLKGVASVV PQRTLDYAEN LRTVRPDFVV HGDDWQTGVQ RHTRERVIEV LSEWGGKLVE
     IPYTPGISST RLHSSVKEVG TTPNVRLSRL RRLLDSKDIV RILEVHNGLT GLIIENSKVT
     VDNQAREFDG MWSSSLTDSL ARGKPDTEAV DVSSRLQMVN ELFEVTTKPL VFDGDTGGKP
     EHFGFTVRSL ERLGVSAVIV EDKEGLKRNS LFGTDVPQTQ SSVEDFSERI RIGKRAQITD
     DFMVIARIES LILEKGMADA VHRAEAYVDA GADGIMIHSR QSDPAEIFEF CRYFDKLPRR
     VPLVVVPTSY SSVRESELAD AGVNMVIYAN HLMRAVYPQV TKVVQSILQH GRAHEAESML
     ASIKDALSII PENAG
//