PATN_ASPCL
ID PATN_ASPCL Reviewed; 259 AA.
AC A1CFM1;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Isoepoxydon dehydrogenase patN {ECO:0000303|PubMed:19383676};
DE Short=IDH {ECO:0000303|PubMed:19383676};
DE EC=1.1.1.- {ECO:0000250|UniProtKB:A0A075TRB3};
DE AltName: Full=Patulin synthesis protein N {ECO:0000303|PubMed:19383676};
GN Name=patN {ECO:0000303|PubMed:19383676}; ORFNames=ACLA_093690;
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: Isoepoxydon dehydrogenase; 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 (By similarity). PatN catalyzes the
CC conversion of isoepoxydon into phyllostine (By similarity). The pathway
CC begins with the synthesis of 6-methylsalicylic acid by the polyketide
CC synthase (PKS) patK via condensation of acetate and malonate units. The
CC 6-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:19383676) (Probable).
CC {ECO:0000250|UniProtKB:A0A075TRB3, ECO:0000305|PubMed:19383676}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=isoepoxydon + NADP(+) = H(+) + NADPH + phyllostine;
CC Xref=Rhea:RHEA:62216, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:145109, ChEBI:CHEBI:145110;
CC Evidence={ECO:0000250|UniProtKB:A0A075TRB3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62217;
CC Evidence={ECO:0000250|UniProtKB:A0A075TRB3};
CC -!- PATHWAY: Mycotoxin biosynthesis; patulin biosynthesis.
CC {ECO:0000305|PubMed:19383676}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:A0A075TRB3}.
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 short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; DS027052; EAW11670.1; -; Genomic_DNA.
DR RefSeq; XP_001273096.1; XM_001273095.1.
DR AlphaFoldDB; A1CFM1; -.
DR SMR; A1CFM1; -.
DR STRING; 5057.CADACLAP00008600; -.
DR EnsemblFungi; EAW11670; EAW11670; ACLA_093690.
DR GeneID; 4704858; -.
DR KEGG; act:ACLA_093690; -.
DR VEuPathDB; FungiDB:ACLA_093690; -.
DR eggNOG; KOG0725; Eukaryota.
DR HOGENOM; CLU_010194_1_2_1; -.
DR OMA; AKDFGRW; -.
DR OrthoDB; 1194344at2759; -.
DR UniPathway; UPA00918; -.
DR Proteomes; UP000006701; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; ISS:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; ISS:GO_Central.
DR GO; GO:0140723; P:patulin biosynthetic process; ISS:GO_Central.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; NAD; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..259
FT /note="Isoepoxydon dehydrogenase patN"
FT /id="PRO_0000437120"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 13..21
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 40..41
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 68..70
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 158..162
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 191..193
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 259 AA; 28138 MW; FAF18E64939AFF2D CRC64;
MVLATSLKGA HVLITGGTRG MGEAMVHQFL QEEANVSYCA RTVTNTEFDE FYKTLPEGNT
ARAVGTAFNV ASKEAIVDWV KSSAERLGRI DVIIANASPM HMEGETEHWV ESFAIDVMGF
VELVRAATPY LEQSPQASII VQSSFMGREF YRSPPAAYGP CKAAQLQHVQ ELSHYLGPKG
IRVNAISPGP ILCKGGPWEK YSTLMPEWVE EQRLKIPLKR LGGPTEVANV AVFLASPLAS
FVTGTNVLVD GGIHVGTQF
