ID   TPCI_ASPFU              Reviewed;         445 AA.
AC   Q4WQY9;
DT   07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2005, sequence version 1.
DT   25-MAY-2022, entry version 62.
DE   RecName: Full=Questin oxidase {ECO:0000250|UniProtKB:Q0CCX5};
DE            EC=1.-.-.- {ECO:0000250|UniProtKB:Q0CCX5};
DE   AltName: Full=Trypacidin synthesis protein K {ECO:0000303|PubMed:26278536};
GN   Name=tpcI {ECO:0000303|PubMed:26242966};
GN   Synonyms=tynI {ECO:0000303|PubMed:26278536}; ORFNames=AFUA_4G14500;
OS   Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS   A1100) (Aspergillus fumigatus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Fumigati.
OX   NCBI_TaxID=330879;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX   PubMed=16372009; DOI=10.1038/nature04332;
RA   Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA   Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA   Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA   Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA   Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA   Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA   Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA   Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA   Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA   Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA   O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA   Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA   Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA   Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA   Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA   Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA   Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA   Barrell B.G., Denning D.W.;
RT   "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT   Aspergillus fumigatus.";
RL   Nature 438:1151-1156(2005).
RN   [2]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=22319557; DOI=10.1371/journal.pone.0029906;
RA   Gauthier T., Wang X., Sifuentes Dos Santos J., Fysikopoulos A., Tadrist S.,
RA   Canlet C., Artigot M.P., Loiseau N., Oswald I.P., Puel O.;
RT   "Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic
RT   to lung cells.";
RL   PLoS ONE 7:E29906-E29906(2012).
RN   [3]
RP   FUNCTION.
RX   PubMed=26278536; DOI=10.1007/s00253-015-6898-1;
RA   Mattern D.J., Schoeler H., Weber J., Novohradska S., Kraibooj K.,
RA   Dahse H.M., Hillmann F., Valiante V., Figge M.T., Brakhage A.A.;
RT   "Identification of the antiphagocytic trypacidin gene cluster in the human-
RT   pathogenic fungus Aspergillus fumigatus.";
RL   Appl. Microbiol. Biotechnol. 99:10151-10161(2015).
RN   [4]
RP   FUNCTION.
RX   PubMed=26242966; DOI=10.1111/1462-2920.13007;
RA   Throckmorton K., Lim F.Y., Kontoyiannis D.P., Zheng W., Keller N.P.;
RT   "Redundant synthesis of a conidial polyketide by two distinct secondary
RT   metabolite clusters in Aspergillus fumigatus.";
RL   Environ. Microbiol. 18:246-259(2016).
CC   -!- FUNCTION: Questin oxidase; part of the gene cluster that mediates the
CC       biosynthesis of trypacidin, a mycotoxin with antiprotozoal activity and
CC       that plays a role in the infection process (PubMed:26278536,
CC       PubMed:26242966). The pathway begins with the synthesis of atrochrysone
CC       thioester by the polyketide synthase (PKS) tpcC (PubMed:26242966). The
CC       atrochrysone carboxyl ACP thioesterase tpcB then breaks the thioester
CC       bond and releases the atrochrysone carboxylic acid from tpcC
CC       (PubMed:26242966). The decarboxylase tpcK converts atrochrysone
CC       carboxylic acid to atrochrysone which is further reduced into emodin
CC       anthrone (PubMed:26242966). The next step is performed by the emodin
CC       anthrone oxygenase tpcL that catalyzes the oxidation of emodinanthrone
CC       to emodin (PubMed:26242966). Emodin O-methyltransferase encoded by tpcA
CC       catalyzes methylation of the 8-hydroxy group of emodin to form questin
CC       (PubMed:26242966). Ring cleavage of questin by questin oxidase tpcI
CC       leads to desmethylsulochrin via several intermediates including questin
CC       epoxide (By similarity). Another methylation step catalyzed by tpcM
CC       leads to the formation of sulochrin which is further converted to
CC       monomethylsulfochrin by tpcH. Finally, the tpcJ catalyzes the
CC       conversion of monomethylsulfochrin to trypacidin (PubMed:26242966).
CC       Trypacidin is toxic for human pulmonary and bronchial epithelial cells
CC       by initiating the intracellular formation of nitric oxide (NO) and
CC       hydrogen peroxide (H(2)O(2)), thus triggering host necrotic cell death
CC       (PubMed:22319557). The trypacidin pathway is also able to produce
CC       endocrocin via a distinct route from the endocrocin Enc pathway
CC       (PubMed:26242966). {ECO:0000250|UniProtKB:Q0CCX8,
CC       ECO:0000269|PubMed:22319557, ECO:0000269|PubMed:26242966,
CC       ECO:0000269|PubMed:26278536}.
CC   -!- COFACTOR:
CC       Name=NADPH; Xref=ChEBI:CHEBI:57783;
CC         Evidence={ECO:0000250|UniProtKB:Q0CCX5};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:26242966}.
CC   -!- TISSUE SPECIFICITY: Specifically expressed in conidia
CC       (PubMed:22319557). {ECO:0000305|PubMed:22319557}.
CC   -!- SIMILARITY: Belongs to the questin oxidase family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AAHF01000005; EAL89345.1; -; Genomic_DNA.
DR   RefSeq; XP_751383.1; XM_746290.1.
DR   AlphaFoldDB; Q4WQY9; -.
DR   EnsemblFungi; EAL89345; EAL89345; AFUA_4G14500.
DR   GeneID; 3509607; -.
DR   KEGG; afm:AFUA_4G14500; -.
DR   VEuPathDB; FungiDB:Afu4g14500; -.
DR   eggNOG; ENOG502S69W; Eukaryota.
DR   HOGENOM; CLU_019145_2_1_1; -.
DR   InParanoid; Q4WQY9; -.
DR   OMA; IDFFYMH; -.
DR   OrthoDB; 614605at2759; -.
DR   Proteomes; UP000002530; Chromosome 4.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IGC:AspGD.
DR   InterPro; IPR025337; Questin_oxidase-like.
DR   PANTHER; PTHR35870; PTHR35870; 1.
DR   Pfam; PF14027; Questin_oxidase; 1.
PE   2: Evidence at transcript level;
KW   Oxidoreductase; Reference proteome.
FT   CHAIN           1..445
FT                   /note="Questin oxidase"
FT                   /id="PRO_0000437101"
SQ   SEQUENCE   445 AA;  49467 MW;  8B8D08C41DF03C78 CRC64;
     MATASQIRLR PRLGVARATD TNPDGALEAA NRLLQKNHNE HHMFWRSVAG HNHVAHSVLN
     TLALGGGPGD LQRAFDDGAE IQVPIPPMDR DAAASLSTPD QFRARMGSLE QYPNFLVFFT
     KEIETRGYPA VVIEYCFSGT SIAESMFANL FEGLYHPLIH LALGIEFDQP SIVAEGLAQA
     ACHDSMNIEP FLFGTDKLAK TQDAPIDLNT PLLSLFHAVR DNEVLRAAAH RDHGDGVARV
     RDGILGRARE EISLIAARFR VDVDELDHRA AEMISCAAYL AGSAQRPGKA RKIDFFHLHA
     VTASLGLIVL LQQPWVTPEQ KARLIEWKAR VDLVWYAASG AVELRRKDIV DYRPRHGLTW
     DSLYQAVRRV HDDGHLAKFI RALKAGEQIS RPFEQGKRAE AFPIKGSMWL RIAQMAYDSS
     AGRPIEEKWI WGAGFEPNWA TVPAV