PATO_ASPCL
ID PATO_ASPCL Reviewed; 572 AA.
AC A1CFM2;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=FAD-linked oxidoreductase patO {ECO:0000303|PubMed:19383676};
DE EC=1.-.-.- {ECO:0000250|UniProtKB:A0A075TR33};
DE AltName: Full=Patulin synthesis protein O {ECO:0000303|PubMed:19383676};
DE Flags: Precursor;
GN Name=patO {ECO:0000303|PubMed:19383676}; ORFNames=ACLA_093700;
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: FAD-linked oxidoreductase; 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). PatO acts with
CC patJ in the vacuole to convert gentisyl alcohol to isoepoxydon (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:A0A075TR33, ECO:0000305|PubMed:19383676}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Mycotoxin biosynthesis; patulin biosynthesis.
CC {ECO:0000305|PubMed:19383676}.
CC -!- SUBCELLULAR LOCATION: Vacuole lumen {ECO:0000250|UniProtKB:A0A075TR33}.
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 oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; DS027052; EAW11671.1; -; Genomic_DNA.
DR RefSeq; XP_001273097.1; XM_001273096.1.
DR AlphaFoldDB; A1CFM2; -.
DR SMR; A1CFM2; -.
DR STRING; 5057.CADACLAP00008669; -.
DR EnsemblFungi; EAW11671; EAW11671; ACLA_093700.
DR GeneID; 4704859; -.
DR KEGG; act:ACLA_093700; -.
DR VEuPathDB; FungiDB:ACLA_093700; -.
DR eggNOG; ENOG502R8I5; Eukaryota.
DR HOGENOM; CLU_018354_4_2_1; -.
DR OMA; NEADPQQ; -.
DR OrthoDB; 1049549at2759; -.
DR UniPathway; UPA00918; -.
DR Proteomes; UP000006701; Unassembled WGS sequence.
DR GO; GO:0005775; C:vacuolar lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005773; C:vacuole; ISS:GO_Central.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0140723; P:patulin biosynthetic process; IMP:GO_Central.
DR Gene3D; 3.30.465.10; -; 2.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Glycoprotein; Oxidoreductase; Reference proteome;
KW Signal; Vacuole.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..572
FT /note="FAD-linked oxidoreductase patO"
FT /evidence="ECO:0000255"
FT /id="PRO_5002633132"
FT DOMAIN 115..295
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 354
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 381
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 422
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 446
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 481
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 572 AA; 62319 MW; 71F4FBC9485B108E CRC64;
MRLSIYSSIL LLRAMCLVRP TFGFPATTCR CMPGDSCWPS STDWAHFNAS IGGRLIATQP
LAQACHDPYY NETECQYLQK HWTLPALHDI SPSSIMAAAV AKDTCDAFTP RSKPCAPGDM
VVYSVNASSP DDFSRTIRFS QQRNIRLVIR NTGHDYLGKS TGAGALSIWT HYLKDIEFVN
YTSSSYTGPA FTMAAGVQGS DIYNVANGRG LVVVGGECAS VGPVGGYTQG GGHSALSSRF
GLAADQVLEW QVVDGTGRLL TASPTQNPDL YWALSGGGGG TYGVVYSMTV KAFPDFPVTG
VVLQFDTKNT SSKDFFQAVS YYHRDLPTYT AAGGMAIAQI TRSSFLLTPL TLPNKTTEEA
RSLIAPFIHE LETLHIPYQL NITQSATYLE HYKKLIEPNP TQLVQNGQYG GRLLPLNVIE
SNNTQLTEAV KTITQDGVVF VGIGLNVSSS VVGDVWNSVL PAWRTAALSV LLSTDWPAGA
NRSTMKTLAD RMTSKWVPIL TALSPDSGCY MNEADPQQPD WPQTFYGRNY ETLYAIKKRY
DPFDTFYAST AVGSGDWQVK TDGRLCRVKG NT
