FOM1_STRWE
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 03-AUG-2022, entry version 86.
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; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC 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=H(+) + phosphoenolpyruvate = 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_JNWK01000026.1.
DR PDB; 5X3D; X-ray; 1.93 A; A=1-139.
DR PDBsum; 5X3D; -.
DR AlphaFoldDB; P96074; -.
DR SMR; P96074; -.
DR KEGG; ag:BAA32495; -.
DR BioCyc; MetaCyc:MON-13657; -.
DR UniPathway; UPA01071; -.
DR GO; GO:0016779; F:nucleotidyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0050188; F:phosphoenolpyruvate mutase activity; IEA:UniProtKB-EC.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR CDD; cd00377; ICL_PEPM; 1.
DR Gene3D; 3.20.20.60; -; 1.
DR Gene3D; 3.40.50.620; -; 1.
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 Pfam; PF01467; CTP_transf_like; 1.
DR SUPFAM; SSF51621; SSF51621; 1.
DR TIGRFAMs; TIGR00125; cyt_tran_rel; 1.
DR TIGRFAMs; TIGR02320; PEP_mutase; 1.
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 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
