PATD_ASPCL
ID PATD_ASPCL Reviewed; 388 AA.
AC A1CFL1;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Alcohol dehydrogenase patD {ECO:0000303|PubMed:19383676};
DE EC=1.1.1.- {ECO:0000250|UniProtKB:A0A075TMP0};
DE AltName: Full=Patulin synthesis protein D {ECO:0000303|PubMed:19383676};
GN Name=patD {ECO:0000303|PubMed:19383676}; ORFNames=ACLA_093590;
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: Alcohol dehydrogenase; part of the gene cluster that mediates
CC the biosynthesis of patulin, an acetate-derived tetraketide mycotoxin
CC produced by several fungal species that shows antimicrobial properties
CC against several bacteria (By similarity). PatD catalyzes the conversion
CC of neopatulin into E-ascladiol (By similarity). The pathway begins with
CC 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:19383676) (Probable).
CC {ECO:0000250|UniProtKB:A0A075TMP0, ECO:0000305|PubMed:19383676}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + neopatulin = (E)-ascladiol + NADP(+);
CC Xref=Rhea:RHEA:62224, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:145111, ChEBI:CHEBI:145112;
CC Evidence={ECO:0000250|UniProtKB:A0A075TMP0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62225;
CC Evidence={ECO:0000250|UniProtKB:A0A075TMP0};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q96533};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q96533};
CC -!- PATHWAY: Mycotoxin biosynthesis; patulin biosynthesis.
CC {ECO:0000305|PubMed:19383676}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:A0A075TMP0}.
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 zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; DS027052; EAW11660.1; -; Genomic_DNA.
DR RefSeq; XP_001273086.1; XM_001273085.1.
DR AlphaFoldDB; A1CFL1; -.
DR SMR; A1CFL1; -.
DR STRING; 5057.CADACLAP00008386; -.
DR EnsemblFungi; EAW11660; EAW11660; ACLA_093590.
DR GeneID; 4704848; -.
DR KEGG; act:ACLA_093590; -.
DR VEuPathDB; FungiDB:ACLA_093590; -.
DR eggNOG; KOG0023; Eukaryota.
DR HOGENOM; CLU_026673_20_1_1; -.
DR OMA; QYPGGYA; -.
DR OrthoDB; 1186407at2759; -.
DR UniPathway; UPA00918; -.
DR Proteomes; UP000006701; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; ISS:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; ISS:GO_Central.
DR GO; GO:0140723; P:patulin biosynthetic process; ISS:GO_Central.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Metal-binding; NAD; NADP; Oxidoreductase; Reference proteome;
KW Zinc.
FT CHAIN 1..388
FT /note="Alcohol dehydrogenase patD"
FT /id="PRO_0000437114"
FT BINDING 46
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q96533"
FT BINDING 47
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q96533"
FT BINDING 67
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00327"
FT BINDING 67
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q96533"
FT BINDING 68
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q96533"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96533"
FT BINDING 104
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96533"
FT BINDING 112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96533"
FT BINDING 198..203
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q96533"
FT BINDING 295..297
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q96533"
FT BINDING 320..322
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q96533"
SQ SEQUENCE 388 AA; 41701 MW; B198DF097329C0F5 CRC64;
MGSTLPTTYK RAFFEKQDAT LTLEEVQLIE PQRGEILVKV EACGVCHSDH FAQMNLMGGG
FPRVPGHEVV GRVAAVGDGE TYWKIGDRTG AGWHGGHDGT CGACKKGLFQ MCDNEQVNGI
TRDGGYAEYV LIRSEAAVRI PDHVNAAKYA PMLCAGVTVF NSIRQMNIPV GETVVIQGLG
GLGHLALQYA NRFGYRVVAL SRGAQKEEFA RKLGAHVYID TSKEDPVAAL QKLGGAALIV
STAPSPELIN PLIEGLGVLG KLLILSIVGG IEVHTGLLVS ERRIAIHRTN SIVRSLLTNS
KVGKGKSIWS WPSGHATDSE EAIAFAELQG IDCLVEEFPL EKCNEAFGRS SSTTADRERV
FLADFTGLTT TAAMMDGSVR FRAVITME
