PATI_PENEN
ID PATI_PENEN Reviewed; 526 AA.
AC A0A075TMP8;
DT 05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT 29-OCT-2014, sequence version 1.
DT 03-AUG-2022, entry version 29.
DE RecName: Full=Cytochrome P450 monooxygenase patI {ECO:0000303|PubMed:25120234};
DE EC=1.-.-.- {ECO:0000269|PubMed:30680886};
DE AltName: Full=Patulin biosynthesis cluster protein I {ECO:0000303|PubMed:25120234};
DE AltName: Full=m-hydroxybenzyl alcohol hydroxylase {ECO:0000303|PubMed:25120234};
GN Name=patI {ECO:0000303|PubMed:25120234}; ORFNames=PEX2_082860;
OS Penicillium expansum (Blue mold rot fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=27334;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, AND INDUCTION.
RC STRAIN=NRRL 35695;
RX PubMed=25120234; DOI=10.1016/j.ijfoodmicro.2014.07.028;
RA Tannous J., El Khoury R., Snini S.P., Lippi Y., El Khoury A., Atoui A.,
RA Lteif R., Oswald I.P., Puel O.;
RT "Sequencing, physical organization and kinetic expression of the patulin
RT biosynthetic gene cluster from Penicillium expansum.";
RL Int. J. Food Microbiol. 189C:51-60(2014).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MD-8;
RX PubMed=25338147; DOI=10.1094/MPMI-09-14-0261-FI;
RA Ballester A.R., Marcet-Houben M., Levin E., Sela N., Selma-Lazaro C.,
RA Carmona L., Wisniewski M., Droby S., Gonzalez-Candelas L., Gabaldon T.;
RT "Genome, transcriptome, and functional analyses of Penicillium expansum
RT provide new insights into secondary metabolism and pathogenicity.";
RL Mol. Plant Microbe Interact. 28:232-248(2015).
RN [3]
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 [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).
RN [6]
RP INDUCTION.
RX PubMed=27528575; DOI=10.1111/mpp.12469;
RA Kumar D., Barad S., Chen Y., Luo X., Tannous J., Dubey A., Glam Matana N.,
RA Tian S., Li B., Keller N., Prusky D.;
RT "LaeA regulation of secondary metabolism modulates virulence in Penicillium
RT expansum and is mediated by sucrose.";
RL Mol. Plant Pathol. 18:1150-1163(2017).
RN [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=30100914; DOI=10.3389/fpls.2018.01094;
RA Kumar D., Tannous J., Sionov E., Keller N., Prusky D.;
RT "Apple intrinsic factors modulating the global regulator, LaeA, the patulin
RT gene cluster and patulin accumulation during fruit colonization by
RT Penicillium expansum.";
RL Front. Plant Sci. 9:1094-1094(2018).
RN [8]
RP FUNCTION, AND INDUCTION.
RX PubMed=25625822; DOI=10.1094/mpmi-12-14-0398-fi;
RA Li B., Zong Y., Du Z., Chen Y., Zhang Z., Qin G., Zhao W., Tian S.;
RT "Genomic characterization reveals insights into patulin biosynthesis and
RT pathogenicity in Penicillium species.";
RL Mol. Plant Microbe Interact. 28:635-647(2015).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY,
RP INDUCTION, AND PATHWAY.
RX PubMed=30680886; DOI=10.1111/1462-2920.14542;
RA Li B., Chen Y., Zong Y., Shang Y., Zhang Z., Xu X., Wang X., Long M.,
RA Tian S.;
RT "Dissection of patulin biosynthesis, spatial control and regulation
RT mechanism in Penicillium expansum.";
RL Environ. Microbiol. 21:1124-1139(2019).
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:30100914, PubMed:25625822,
CC PubMed:30680886). PatI catalyzes the conversion of m-hydroxybenzyl
CC alcohol into gentisyl alcohol (PubMed:30680886). The pathway begins
CC with the synthesis of 6-methylsalicylic acid by the polyketide synthase
CC (PKS) patK via condensation of acetate and malonate units. The 6-
CC methylsalicylic acid decarboxylase patG then catalyzes the
CC decarboxylation of 6-methylsalicylic acid to yield m-cresol (also known
CC as 3-methylphenol). These first reactions occur in the cytosol. The
CC intermediate m-cresol is then transported into the endoplasmic
CC reticulum where the cytochrome P450 monooxygenase patH converts it to
CC m-hydroxybenzyl alcohol, which is further converted to gentisyl alcohol
CC by the cytochrome P450 monooxygenase patI. The oxidoreductases patJ and
CC patO further convert gentisyl alcohol to isoepoxydon in the vacuole.
CC PatN catalyzes then the transformation of isoepoxydon into phyllostine.
CC The cluster protein patF is responsible for the conversion from
CC phyllostine to neopatulin whereas the alcohol dehydrogenase patD
CC converts neopatulin to E-ascladiol. The steps between isoepoxydon and
CC E-ascladiol occur in the cytosol, and E-ascladiol is probably secreted
CC to the extracellular space by one of the cluster-specific transporters
CC patC or patM. Finally, the secreted patulin synthase patE catalyzes the
CC conversion of E-ascladiol to patulin (PubMed:30680886) (Probable).
CC {ECO:0000269|PubMed:25625822, ECO:0000269|PubMed:30100914,
CC ECO:0000269|PubMed:30680886, ECO:0000305|PubMed:30680886}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxybenzyl alcohol + O2 + reduced [NADPH--hemoprotein
CC reductase] = gentisyl alcohol + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:62212, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:5325, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17069,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:30680886};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62213;
CC Evidence={ECO:0000269|PubMed:30680886};
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:30680886}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:30680886}; Single-pass membrane protein
CC {ECO:0000269|PubMed:30680886}.
CC -!- INDUCTION: Expression is correlated with the production of patulin
CC (PubMed:25120234). Expression is positively regulated by the secondary
CC metabolism regulator laeA (PubMed:27528575, PubMed:30100914).
CC Expression is strongly decreased with increased sucrose concentrations.
CC This decrease is lost in the presence of malic acid (PubMed:30100914).
CC Expression is increased with pH changes from 2.5 to 3.5 in the presence
CC of a limiting concentration of sucrose, 50 mM (PubMed:30100914).
CC Natural phenols present in apple fruits such as chlorogenic acid or the
CC flavonoid epicatechin modulate patulin biosynthesis. They increase
CC expression in the absence of sucrose, have little impact in the
CC presence of 15 mM sucrose, and decrease expression in 175 mM sucrose
CC (PubMed:30100914). Expression is positively regulated by the patulin
CC cluster-specific transcription factor patL (PubMed:25625822). Finally,
CC expression is also positively regulated by the velvet family proteins
CC transcription regulators veA, velB, velC, but not vosA
CC (PubMed:30680886). {ECO:0000269|PubMed:25120234,
CC ECO:0000269|PubMed:25625822, ECO:0000269|PubMed:27528575,
CC ECO:0000269|PubMed:30100914, ECO:0000269|PubMed:30680886}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of patulin
CC and shows significant slower colony expansion.
CC {ECO:0000269|PubMed:30680886}.
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}.
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DR EMBL; KF899892; AIG62145.1; -; Genomic_DNA.
DR EMBL; JQFZ01000262; KGO52639.1; -; Genomic_DNA.
DR RefSeq; XP_016595369.1; XM_016745556.1.
DR AlphaFoldDB; A0A075TMP8; -.
DR SMR; A0A075TMP8; -.
DR EnsemblFungi; KGO43543; KGO43543; PEXP_094440.
DR EnsemblFungi; KGO51503; KGO51503; PEX1_002410.
DR EnsemblFungi; KGO52639; KGO52639; PEX2_082860.
DR GeneID; 27680976; -.
DR HOGENOM; CLU_001570_2_1_1; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; A0A075TMP8; -.
DR UniPathway; UPA00918; -.
DR Proteomes; UP000030143; Unassembled WGS sequence.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA: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; Iron; Membrane; Metal-binding;
KW Monooxygenase; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..526
FT /note="Cytochrome P450 monooxygenase patI"
FT /id="PRO_0000445922"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 7..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..526
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT BINDING 446
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 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 526 AA; 60437 MW; 41F2E6AD31CA4B57 CRC64;
MDILQLAPTH LLAILLSSTS ALFLITYLLR AGHRPSDLPN GPPTVPLFGN ELQVPKSDAH
FQFSRWAKEY GGFFTLKRYN NTTIVISDQK LIKTLLDKKS NIYSHRPASL VSHLITQSDH
LLVMQYGERW RMLRKTIHQY FMEPRCERDH WKVQEAEAKQ MLHDYLTMPE DHMLHPKRYS
NSITNSLVFG IRTKTVHDEY MKKLFYLMDK WSLVQELGAT PPVDSFALLR YVPQWMLGNW
RNRAVEVGDL MQSLYQTVLD QVKERRQRGI QRDSFMDRVL DTLKQTPLSE NELRFLGGVL
MEGGSDTSSS LILTIIQAMT KYPEVQAKAH AQIDSIIGHN RSPAWSDWSK LPYINMIIKE
SHRWRPVSPL GVPHAVAEDD HIDGKLIPQG SSIVLNVWGM HHDSDRWQEP EHFQPERFAD
FPALASGYAG SERRDHLGYG AGRRICPGIH LAERNLIIGI AKLLWAFEFL EPLGSDSDIS
AHSGASKGFL HCPKDYGCVI RLRSPEKRET IMREFAEAQE VFARFD
