ID   GEDK_ASPTN              Reviewed;         446 AA.
AC   Q0CCX5;
DT   07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 51.
DE   RecName: Full=Questin oxidase {ECO:0000303|PubMed:3182756};
DE            EC=1.14.13.43 {ECO:0000269|PubMed:3182756};
DE   AltName: Full=Geodin synthesis protein K {ECO:0000303|PubMed:24009710};
GN   Name=gedK {ECO:0000303|PubMed:24009710}; ORFNames=ATEG_08459;
OS   Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=341663;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=NIH 2624 / FGSC A1156;
RA   Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA   Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA   Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA   Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA   Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA   Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA   Nierman W.C., Milne T., Madden K.;
RT   "Annotation of the Aspergillus terreus NIH2624 genome.";
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=3182756; DOI=10.1093/oxfordjournals.jbchem.a122365;
RA   Fujii I., Ebizuka Y., Sankawa U.;
RT   "A novel anthraquinone ring cleavage enzyme from Aspergillus terreus.";
RL   J. Biochem. 103:878-883(1988).
RN   [3]
RP   FUNCTION.
RX   PubMed=1810248;
RA   Fujii I., Chen Z.G., Ebizuka Y., Sankawa U.;
RT   "Identification of emodinanthrone oxygenase in fungus Aspergillus
RT   terreus.";
RL   Biochem. Int. 25:1043-1049(1991).
RN   [4]
RP   FUNCTION.
RX   PubMed=1444712; DOI=10.1007/bf00249062;
RA   Chen Z.G., Fujii I., Ebizuka Y., Sankawa U.;
RT   "Emodin O-methyltransferase from Aspergillus terreus.";
RL   Arch. Microbiol. 158:29-34(1992).
RN   [5]
RP   FUNCTION.
RX   PubMed=7665560; DOI=10.1074/jbc.270.37.21495;
RA   Huang K.X., Fujii I., Ebizuka Y., Gomi K., Sankawa U.;
RT   "Molecular cloning and heterologous expression of the gene encoding
RT   dihydrogeodin oxidase, a multicopper blue enzyme from Aspergillus
RT   terreus.";
RL   J. Biol. Chem. 270:21495-21502(1995).
RN   [6]
RP   FUNCTION.
RX   PubMed=12536215; DOI=10.1038/nbt781;
RA   Askenazi M., Driggers E.M., Holtzman D.A., Norman T.C., Iverson S.,
RA   Zimmer D.P., Boers M.E., Blomquist P.R., Martinez E.J., Monreal A.W.,
RA   Feibelman T.P., Mayorga M.E., Maxon M.E., Sykes K., Tobin J.V., Cordero E.,
RA   Salama S.R., Trueheart J., Royer J.C., Madden K.T.;
RT   "Integrating transcriptional and metabolite profiles to direct the
RT   engineering of lovastatin-producing fungal strains.";
RL   Nat. Biotechnol. 21:150-156(2003).
RN   [7]
RP   FUNCTION.
RX   PubMed=19549600; DOI=10.1016/j.chembiol.2009.04.004;
RA   Awakawa T., Yokota K., Funa N., Doi F., Mori N., Watanabe H.,
RA   Horinouchi S.;
RT   "Physically discrete beta-lactamase-type thioesterase catalyzes product
RT   release in atrochrysone synthesis by iterative type I polyketide
RT   synthase.";
RL   Chem. Biol. 16:613-623(2009).
RN   [8]
RP   FUNCTION.
RX   PubMed=24009710; DOI=10.1371/journal.pone.0072871;
RA   Nielsen M.T., Nielsen J.B., Anyaogu D.C., Holm D.K., Nielsen K.F.,
RA   Larsen T.O., Mortensen U.H.;
RT   "Heterologous reconstitution of the intact geodin gene cluster in
RT   Aspergillus nidulans through a simple and versatile PCR based approach.";
RL   PLoS ONE 8:E72871-E72871(2013).
CC   -!- FUNCTION: Questin oxidase; part of the gene cluster that mediates the
CC       biosynthesis of geodin, an intermediate in the biosynthesis of other
CC       natural products (PubMed:7665560, PubMed:19549600, PubMed:24009710).
CC       The pathway begins with the synthesis of atrochrysone thioester by the
CC       polyketide synthase (PKS) gedC (PubMed:12536215, PubMed:19549600). The
CC       atrochrysone carboxyl ACP thioesterase gedB then breaks the thioester
CC       bond and releases the atrochrysone carboxylic acid from gedC
CC       (PubMed:19549600). The atrochrysone carboxylic acid is then converted
CC       to atrochrysone which is further transformed into emodinanthrone
CC       (PubMed:24009710). The next step is performed by the emodinanthrone
CC       oxygenase gedH that catalyzes the oxidation of emodinanthrone to emodin
CC       (PubMed:1810248). Emodin O-methyltransferase encoded probably by gedA
CC       then catalyzes methylation of the 8-hydroxy group of emodin to form
CC       questin (PubMed:1444712). Ring cleavage of questin by questin oxidase
CC       gedK leads to desmethylsulochrin via several intermediates including
CC       questin epoxide (PubMed:3182756). Another methylation step probably
CC       catalyzed by methyltransferase gedG leads to the formation of sulochrin
CC       which is further converted to dihydrogeodin by the sulochrin halogenase
CC       gedL (PubMed:24009710). Finally, the dihydrogeodin oxidase gedJ
CC       catalyzes the stereospecific phenol oxidative coupling reaction
CC       converting dihydrogeodin to geodin (PubMed:7665560).
CC       {ECO:0000269|PubMed:12536215, ECO:0000269|PubMed:1444712,
CC       ECO:0000269|PubMed:1810248, ECO:0000269|PubMed:19549600,
CC       ECO:0000269|PubMed:24009710, ECO:0000269|PubMed:3182756,
CC       ECO:0000269|PubMed:7665560}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=NADPH + O2 + questin = demethylsulochrin + NADP(+);
CC         Xref=Rhea:RHEA:10836, ChEBI:CHEBI:15379, ChEBI:CHEBI:57676,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:77886;
CC         EC=1.14.13.43; Evidence={ECO:0000269|PubMed:3182756};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10837;
CC         Evidence={ECO:0000269|PubMed:3182756};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 2.5. {ECO:0000269|PubMed:3182756};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:3182756}.
CC   -!- SIMILARITY: Belongs to the questin oxidase family. {ECO:0000305}.
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DR   EMBL; CH476605; EAU31632.1; -; Genomic_DNA.
DR   RefSeq; XP_001217598.1; XM_001217597.1.
DR   AlphaFoldDB; Q0CCX5; -.
DR   EnsemblFungi; EAU31632; EAU31632; ATEG_08459.
DR   GeneID; 4353197; -.
DR   VEuPathDB; FungiDB:ATEG_08459; -.
DR   eggNOG; ENOG502S69W; Eukaryota.
DR   HOGENOM; CLU_019145_2_1_1; -.
DR   OMA; IDFFYMH; -.
DR   OrthoDB; 614605at2759; -.
DR   BioCyc; MetaCyc:MON-17514; -.
DR   Proteomes; UP000007963; Unassembled WGS sequence.
DR   GO; GO:0050246; F:questin monooxygenase activity; IEA:UniProtKB-EC.
DR   InterPro; IPR025337; Questin_oxidase-like.
DR   PANTHER; PTHR35870; PTHR35870; 1.
DR   Pfam; PF14027; Questin_oxidase; 1.
PE   1: Evidence at protein level;
KW   Oxidoreductase; Reference proteome.
FT   CHAIN           1..446
FT                   /note="Questin oxidase"
FT                   /id="PRO_0000437099"
SQ   SEQUENCE   446 AA;  49347 MW;  904B354A913028AA CRC64;
     MATATQIFLS PDHAGIARVS ECPVGAIEAA NHLLQTNHDE HHMFWRPVAG HNHLTHSVLT
     ILALGGGPAE LQRAFDDARD IQRPIPPVDR QVVEQLGDPE QFRSRIGQLD QYSNFLAFFS
     QEIATKGYRA VVDEHCFSGS RNAETLFAQL YEGLYHPVIH LAFGIEFEQP SIVAEALAQV
     ASHDSMGIEA FLMDCEAEAT QSAHSGRTLV QLFRDAEADE ALRHAAEGFD DGPARVRDGV
     LGRTARAITA LAAQFRVDPQ DIEHRLAEMI NCSAFITGAV QRTGKPRKID FFHLHTVTAS
     LSIDILVRQP WISPVVKARL VEWKARVDLV WYTATGAVQL HLPSLLNYMP TSSAGMDWAA
     LYRAVAAVHD DGHLAKLVRA LKSGEAVSNP FEKGAGETFP IQGIAWLKLA QMAYDTTVDR
     PIEQKWIWGI GFDENWTHVL SLESEK