PATH_ASPCL
ID PATH_ASPCL Reviewed; 524 AA.
AC A1CFL5;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 64.
DE RecName: Full=Cytochrome P450 monooxygenase patH {ECO:0000303|PubMed:19383676};
DE EC=1.-.-.- {ECO:0000269|PubMed:19383676};
DE AltName: Full=Patulin synthesis protein H {ECO:0000303|PubMed:19383676};
DE AltName: Full=m-cresol hydrolase {ECO:0000303|PubMed:19383676};
GN Name=patH {ECO:0000303|PubMed:19383676};
GN Synonyms=CYP619C3 {ECO:0000303|PubMed:19383676}; ORFNames=ACLA_093630;
OS Aspergillus clavatus (strain ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 /
OS NRRL 1 / QM 1276 / 107).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=344612;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 / NRRL 1;
RX PubMed=18404212; DOI=10.1371/journal.pgen.1000046;
RA Fedorova N.D., Khaldi N., Joardar V.S., Maiti R., Amedeo P., Anderson M.J.,
RA Crabtree J., Silva J.C., Badger J.H., Albarraq A., Angiuoli S., Bussey H.,
RA Bowyer P., Cotty P.J., Dyer P.S., Egan A., Galens K., Fraser-Liggett C.M.,
RA Haas B.J., Inman J.M., Kent R., Lemieux S., Malavazi I., Orvis J.,
RA Roemer T., Ronning C.M., Sundaram J.P., Sutton G., Turner G., Venter J.C.,
RA White O.R., Whitty B.R., Youngman P., Wolfe K.H., Goldman G.H.,
RA Wortman J.R., Jiang B., Denning D.W., Nierman W.C.;
RT "Genomic islands in the pathogenic filamentous fungus Aspergillus
RT fumigatus.";
RL PLoS Genet. 4:E1000046-E1000046(2008).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=15082620; DOI=10.1093/ije/dyh028;
RG Patulin Clinical Trials Committee, Medical Research Council;
RT "Clinical trial of patulin in the common cold. 1944.";
RL Int. J. Epidemiol. 33:243-246(2004).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=19383676; DOI=10.1099/mic.0.024836-0;
RA Artigot M.P., Loiseau N., Laffitte J., Mas-Reguieg L., Tadrist S.,
RA Oswald I.P., Puel O.;
RT "Molecular cloning and functional characterization of two CYP619 cytochrome
RT P450s involved in biosynthesis of patulin in Aspergillus clavatus.";
RL Microbiology 155:1738-1747(2009).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=22222931; DOI=10.1016/j.fct.2011.12.022;
RA de Melo F.T., de Oliveira I.M., Greggio S., Dacosta J.C., Guecheva T.N.,
RA Saffi J., Henriques J.A., Rosa R.M.;
RT "DNA damage in organs of mice treated acutely with patulin, a known
RT mycotoxin.";
RL Food Chem. Toxicol. 50:3548-3555(2012).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=26619846; DOI=10.1007/s13277-015-4474-z;
RA Boussabbeh M., Ben Salem I., Rjiba-Touati K., Bouyahya C., Neffati F.,
RA Najjar M.F., Bacha H., Abid-Essefi S.;
RT "The potential effect of patulin on mice bearing melanoma cells: an anti-
RT tumour or carcinogenic effect?";
RL Tumor Biol. 37:6285-6295(2016).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of patulin, an acetate-derived tetraketide
CC mycotoxin produced by several fungal species that shows antimicrobial
CC properties against several bacteria (PubMed:19383676). PatH catalyzes
CC the conversion of m-cresol into m-hydroxybenzyl alcohol
CC (PubMed:19383676). The pathway begins with the synthesis of 6-
CC methylsalicylic acid by the polyketide synthase (PKS) patK via
CC condensation of acetate and malonate units. The 6-methylsalicylic acid
CC decarboxylase patG then catalyzes the decarboxylation of 6-
CC methylsalicylic acid to yield m-cresol (also known as 3-methylphenol).
CC These first reactions occur in the cytosol. The intermediate m-cresol
CC is then transported into the endoplasmic reticulum where the cytochrome
CC P450 monooxygenase patH converts it to m-hydroxybenzyl alcohol, which
CC is further converted to gentisyl alcohol by the cytochrome P450
CC monooxygenase patI. The oxidoreductases patJ and patO further convert
CC gentisyl alcohol to isoepoxydon in the vacuole. PatN catalyzes then the
CC transformation of isoepoxydon into phyllostine. The cluster protein
CC patF is responsible for the conversion from phyllostine to neopatulin
CC whereas the alcohol dehydrogenase patD converts neopatulin to E-
CC ascladiol. The steps between isoepoxydon and E-ascladiol occur in the
CC cytosol, and E-ascladiol is probably secreted to the extracellular
CC space by one of the cluster-specific transporters patC or patM.
CC Finally, the secreted patulin synthase patE catalyzes the conversion of
CC E-ascladiol to patulin (PubMed:19383676) (Probable).
CC {ECO:0000269|PubMed:19383676, ECO:0000305|PubMed:19383676}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-methylphenol + O2 + reduced [NADPH--hemoprotein reductase] =
CC 3-hydroxybenzyl alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:62208, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17069, ChEBI:CHEBI:17231, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:19383676};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62209;
CC Evidence={ECO:0000269|PubMed:19383676};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis; patulin biosynthesis.
CC {ECO:0000269|PubMed:19383676}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:A0A075TRL5}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- BIOTECHNOLOGY: Patulin was originally used as an antibiotic and
CC specifically trialed to be used against the common cold, but it is no
CC longer used for that purpose since it has been shown to induce
CC immunological, neurological and gastrointestinal effects
CC (PubMed:15082620). Genotoxic effects of patulin with dose-dependent
CC increase in DNA strand breaks in brain, liver and kidneys have been
CC detected in mice (PubMed:22222931). However, more recently, it has been
CC proposed that patulin might also have anti-tumor properties
CC (PubMed:26619846). {ECO:0000269|PubMed:15082620,
CC ECO:0000269|PubMed:22222931, ECO:0000269|PubMed:26619846}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; DS027052; EAW11664.1; -; Genomic_DNA.
DR RefSeq; XP_001273090.1; XM_001273089.1.
DR AlphaFoldDB; A1CFL5; -.
DR SMR; A1CFL5; -.
DR STRING; 344612.A1CFL5; -.
DR PRIDE; A1CFL5; -.
DR EnsemblFungi; EAW11664; EAW11664; ACLA_093630.
DR GeneID; 4704852; -.
DR KEGG; act:ACLA_093630; -.
DR VEuPathDB; FungiDB:ACLA_093630; -.
DR eggNOG; KOG0156; Eukaryota.
DR HOGENOM; CLU_001570_2_1_1; -.
DR OMA; YEMFSRL; -.
DR OrthoDB; 702827at2759; -.
DR UniPathway; UPA00918; -.
DR Proteomes; UP000006701; Unassembled WGS sequence.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IDA:GO_Central.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0140723; P:patulin biosynthetic process; IDA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Heme; Iron; Membrane; Metal-binding;
KW Monooxygenase; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..524
FT /note="Cytochrome P450 monooxygenase patH"
FT /evidence="ECO:0000255"
FT /id="PRO_0000437115"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 5..23
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 24..524
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT BINDING 442
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 499
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 524 AA; 59806 MW; B5A04E7F0607E7AA CRC64;
MEPMLLLILV AAVVLLFVRW AFVYGHRTSN MPKGPPTLPF IGNIHQIPTQ YTHIKFTEWA
AKYGGLYMLK VGNGNMAVVT DRRLVKEVVD RKSGIYSHRP HSFVSHELIT KGNHLLVMHY
GDQWRTFRRL IHQHLMESMV DSQHVKIVNA EAIQLVRDYL VDPEHHMAHP KRFSNSITNS
IVFGIRTADR NGSNMKRLYK LMEEWSEIME TGATPPVDLF PWMKMLPQWM FSNYVNRAKA
IGVQMETLYT DILNKVIKRR NGGQNLGTFM DRVLDGQEKN DLPWHQLAFI GGVLMEGGSD
TSSSLTIAIV QALILNPAVQ KKAHAEIDAV VGSDRSPVWE DLEKLPYINM IIKEGHRWRP
ILPLCFPHAL GEDDWVDGKL LPKGTVVVIN TWGMHMDPSQ PDDPAAFIPE RYANHPQLAP
EYAAGKWENR DHYGYGVGRR ICPGIHLAER NMFLAIAKLL WAFEFQRGEG KIDSDPVTGY
HNGFLYCAKD YPCRPVVRNK TIRATIEREF ATATKEVFSQ FTEG
