PATE_ASPCL
ID PATE_ASPCL Reviewed; 628 AA.
AC A1CFL2;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Patulin synthase {ECO:0000250|UniProtKB:A0A075TRK9};
DE EC=1.1.-.- {ECO:0000250|UniProtKB:A0A075TRK9};
DE AltName: Full=Dehydrogenase patE {ECO:0000303|PubMed:19383676};
DE AltName: Full=Patulin synthesis protein E {ECO:0000303|PubMed:19383676};
DE Flags: Precursor;
GN Name=patE {ECO:0000303|PubMed:19383676}; ORFNames=ACLA_093600;
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.
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: Patulin synthase; part of the gene cluster that mediates the
CC biosynthesis of patulin, an acetate-derived tetraketide mycotoxin
CC produced by several fungal species that shows antimicrobial properties
CC against several bacteria (By similarity). PatE catalyzes the last step
CC of the pathway which is the conversion of E-ascladiol to patulin (By
CC similarity). The pathway begins with the synthesis of 6-methylsalicylic
CC acid by the polyketide synthase (PKS) patK via condensation of acetate
CC and malonate units. The 6-methylsalicylic acid decarboxylase patG then
CC catalyzes the decarboxylation of 6-methylsalicylic acid to yield m-
CC cresol (also known as 3-methylphenol). These first reactions occur in
CC the cytosol. The intermediate m-cresol is then transported into the
CC endoplasmic reticulum where the cytochrome P450 monooxygenase patH
CC converts it to m-hydroxybenzyl alcohol, which is further converted to
CC gentisyl alcohol by the cytochrome P450 monooxygenase patI. The
CC oxidoreductases patJ and patO further convert gentisyl alcohol to
CC isoepoxydon in the vacuole. PatN catalyzes then the transformation of
CC isoepoxydon into phyllostine. The cluster protein patF is responsible
CC for the conversion from phyllostine to neopatulin whereas the alcohol
CC dehydrogenase patD converts neopatulin to E-ascladiol. The steps
CC between isoepoxydon and E-ascladiol occur in the cytosol, and E-
CC ascladiol is probably secreted to the extracellular space by one of the
CC cluster-specific transporters patC or patM. Finally, the secreted
CC patulin synthase patE catalyzes the conversion of E-ascladiol to
CC patulin (PubMed:19383676) (Probable).
CC {ECO:0000250|UniProtKB:A0A075TRK9, ECO:0000305|PubMed:19383676}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(E)-ascladiol + A = AH2 + patulin; Xref=Rhea:RHEA:62228,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:17499, ChEBI:CHEBI:74926,
CC ChEBI:CHEBI:145112; Evidence={ECO:0000250|UniProtKB:A0A075TRK9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62229;
CC Evidence={ECO:0000250|UniProtKB:A0A075TRK9};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:E4QP00};
CC -!- PATHWAY: Mycotoxin biosynthesis; patulin biosynthesis.
CC {ECO:0000305|PubMed:19383676}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q12062}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex
CC {ECO:0000250|UniProtKB:A0A075TRK9}. Vacuole
CC {ECO:0000250|UniProtKB:A0A075TRK9}. Secreted
CC {ECO:0000250|UniProtKB:A0A075TRK9}. Secreted, cell wall
CC {ECO:0000250|UniProtKB:A0A075TRK9}.
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 GMC oxidoreductase family. {ECO:0000305}.
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DR EMBL; DS027052; EAW11661.1; -; Genomic_DNA.
DR RefSeq; XP_001273087.1; XM_001273086.1.
DR AlphaFoldDB; A1CFL2; -.
DR SMR; A1CFL2; -.
DR STRING; 5057.CADACLAP00008472; -.
DR EnsemblFungi; EAW11661; EAW11661; ACLA_093600.
DR GeneID; 4704849; -.
DR KEGG; act:ACLA_093600; -.
DR VEuPathDB; FungiDB:ACLA_093600; -.
DR eggNOG; KOG1238; Eukaryota.
DR HOGENOM; CLU_002865_6_3_1; -.
DR OMA; GPESYAM; -.
DR OrthoDB; 798314at2759; -.
DR UniPathway; UPA00918; -.
DR Proteomes; UP000006701; Unassembled WGS sequence.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0031012; C:extracellular matrix; ISS:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005773; C:vacuole; IEA:UniProtKB-SubCell.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; ISS:GO_Central.
DR GO; GO:0016614; F:oxidoreductase activity, acting on CH-OH group of donors; IEA:InterPro.
DR GO; GO:0140723; P:patulin biosynthetic process; ISS:GO_Central.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR012132; GMC_OxRdtase.
DR InterPro; IPR000172; GMC_OxRdtase_N.
DR InterPro; IPR007867; GMC_OxRtase_C.
DR PANTHER; PTHR11552; PTHR11552; 1.
DR Pfam; PF05199; GMC_oxred_C; 1.
DR Pfam; PF00732; GMC_oxred_N; 1.
DR PIRSF; PIRSF000137; Alcohol_oxidase; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR PROSITE; PS00624; GMC_OXRED_2; 1.
PE 1: Evidence at protein level;
KW Cell wall; Cytoplasm; FAD; Flavoprotein; Glycoprotein; Oxidoreductase;
KW Reference proteome; Secreted; Signal; Vacuole.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..628
FT /note="Patulin synthase"
FT /evidence="ECO:0000255"
FT /id="PRO_5002632926"
FT ACT_SITE 564
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 60..61
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 81..82
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 147..150
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 598
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 609..610
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 260
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 386
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 429
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 486
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 628 AA; 67952 MW; 83D3A7AFF8702C2F CRC64;
MRPIPSILGA LGAFATLSAA APLESTLYGP GASHARSMLG SSFGVPGNQT FDYVVIGGGT
AGLAIASRLA EQGAGTVAVI EAGGFYELNN GNLSQIPAND AYYVGKDLDD WQPGVDWGFH
TVPQAGAYGR ASHYARGKCL GGSSARNYMA YQRGTKSSYQ RWADMVGDQS YAWENFLPFF
EKSLHFTPAN DALRGANATV QYDPAVLGNG QGPLSVTYSH YVQSFATWAQ KAFLEMGLAV
RNCFQSGELL GQSFGMYTIN ATTMHRESSE TSFLRRALAY PNFMVFQSTL AKRILFDGKK
RAVAVQLDTQ GYRYTLTARK EVVLSAGAFQ SPQLLMVSGV GPAATLQQHG IPLVADRPGV
GQNLQDHIIY APSYRVDLIT QSALLNATFE AQANRDYHER AAGIYANPTS DILAWEKIPE
PKRSAWLSNT TRRALAQYPA DWPEIEFLTM GGFFGYQNNY VRDNPSDGYN YASLAVSLCT
PRSRGNVSIA SADAAVPPLI NPNWLTDPVD VELAVAAFKR ARDFFGTSAL KPVLIGDEYF
PGERVATDAQ IEDHVRKSFD TIFHASCTCA MGKREDQMAV VDSKARVIGV DALRVVDASA
FPMLPPGHPQ STIYALAEKI ACDISGAC
