ID   GEDC_ASPTN              Reviewed;        1771 AA.
AC   Q0CCY3;
DT   07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 81.
DE   RecName: Full=Atrochrysone carboxylic acid synthase {ECO:0000303|PubMed:19549600};
DE            Short=ACAS {ECO:0000303|PubMed:19549600};
DE            EC=2.3.1.- {ECO:0000269|PubMed:19549600};
DE   AltName: Full=Geodin synthesis protein C {ECO:0000303|PubMed:24009710};
DE   AltName: Full=Non-reducing polyketide synthase gedC {ECO:0000303|PubMed:19549600};
GN   Name=gedC {ECO:0000303|PubMed:24009710}; ORFNames=ATEG_08451;
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.
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   IDENTIFICATION, FUNCTION, AND DISRUPTION PHENOTYPE.
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   DISRUPTION PHENOTYPE.
RX   PubMed=15129726; DOI=10.1016/j.jbiotec.2003.10.021;
RA   Couch R.D., Gaucher G.M.;
RT   "Rational elimination of Aspergillus terreus sulochrin production.";
RL   J. Biotechnol. 108:171-178(2004).
RN   [8]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
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   [9]
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: Non-reducing polyketide synthase; part of the gene cluster
CC       that mediates the biosynthesis of geodin, an intermediate in the
CC       biosynthesis of other natural products (PubMed:7665560,
CC       PubMed:19549600, PubMed:24009710). The pathway begins with the
CC       synthesis of atrochrysone thioester by the polyketide synthase (PKS)
CC       gedC (PubMed:12536215, PubMed:19549600). The atrochrysone carboxyl ACP
CC       thioesterase gedB then breaks the thioester bond and releases the
CC       atrochrysone carboxylic acid from gedC (PubMed:19549600). The
CC       atrochrysone carboxylic acid is then converted to atrochrysone which is
CC       further transformed into emodinanthrone (PubMed:24009710). The next
CC       step is performed by the emodinanthrone oxygenase gedH that catalyzes
CC       the oxidation of emodinanthrone to emodin (PubMed:1810248). Emodin O-
CC       methyltransferase encoded probably by gedA then catalyzes methylation
CC       of the 8-hydroxy group of emodin to form questin (PubMed:1444712). Ring
CC       cleavage of questin by questin oxidase gedK leads to desmethylsulochrin
CC       via several intermediates including questin epoxide (PubMed:3182756).
CC       Another methylation step probably catalyzed by methyltransferase gedG
CC       leads to the formation of sulochrin which is further converted to
CC       dihydrogeodin by the sulochrin halogenase gedL (PubMed:24009710).
CC       Finally, the dihydrogeodin oxidase gedJ catalyzes the stereospecific
CC       phenol oxidative coupling reaction converting dihydrogeodin to geodin
CC       (PubMed:7665560). {ECO:0000269|PubMed:12536215,
CC       ECO:0000269|PubMed:1444712, ECO:0000269|PubMed:1810248,
CC       ECO:0000269|PubMed:19549600, ECO:0000269|PubMed:24009710,
CC       ECO:0000269|PubMed:3182756, ECO:0000269|PubMed:7665560}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=8 H(+) + holo-[ACP] + 8 malonyl-CoA = atrochrysone carboxyl-
CC         [ACP] + 8 CO2 + 8 CoA + 2 H2O; Xref=Rhea:RHEA:64232, Rhea:RHEA-
CC         COMP:9685, Rhea:RHEA-COMP:16552, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC         ChEBI:CHEBI:57384, ChEBI:CHEBI:64479, ChEBI:CHEBI:149712;
CC         Evidence={ECO:0000269|PubMed:19549600};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64233;
CC         Evidence={ECO:0000269|PubMed:19549600};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:24009710}.
CC   -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC       (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC       repeated decarboxylative condensation to elongate the polyketide
CC       backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC       transfers the extender unit malonyl-CoA; a product template (PT) domain
CC       that controls the immediate cyclization regioselectivity of the
CC       reactive polyketide backbone; and an acyl-carrier protein (ACP) that
CC       serves as the tether of the growing and completed polyketide via its
CC       phosphopantetheinyl arm (By similarity).
CC       {ECO:0000250|UniProtKB:Q5B0D0}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of geodin and of its
CC       intermediary metabolite sulochrin (PubMed:12536215, PubMed:15129726).
CC       {ECO:0000269|PubMed:12536215, ECO:0000269|PubMed:15129726}.
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DR   EMBL; CH476605; EAU31624.1; -; Genomic_DNA.
DR   RefSeq; XP_001217072.1; XM_001217072.1.
DR   AlphaFoldDB; Q0CCY3; -.
DR   SMR; Q0CCY3; -.
DR   STRING; 341663.Q0CCY3; -.
DR   PRIDE; Q0CCY3; -.
DR   EnsemblFungi; EAU31624; EAU31624; ATEG_08451.
DR   GeneID; 4353101; -.
DR   VEuPathDB; FungiDB:ATEG_08451; -.
DR   eggNOG; KOG1202; Eukaryota.
DR   HOGENOM; CLU_000022_6_1_1; -.
DR   OMA; AAYGHKM; -.
DR   OrthoDB; 68112at2759; -.
DR   BioCyc; MetaCyc:MON-21293; -.
DR   Proteomes; UP000007963; Unassembled WGS sequence.
DR   GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR   Gene3D; 1.10.1200.10; -; 1.
DR   Gene3D; 3.10.129.110; -; 1.
DR   Gene3D; 3.40.366.10; -; 2.
DR   Gene3D; 3.40.47.10; -; 1.
DR   InterPro; IPR001227; Ac_transferase_dom_sf.
DR   InterPro; IPR036736; ACP-like_sf.
DR   InterPro; IPR014043; Acyl_transferase.
DR   InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR   InterPro; IPR018201; Ketoacyl_synth_AS.
DR   InterPro; IPR014031; Ketoacyl_synth_C.
DR   InterPro; IPR014030; Ketoacyl_synth_N.
DR   InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR   InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR   InterPro; IPR020807; PKS_dehydratase.
DR   InterPro; IPR042104; PKS_dehydratase_sf.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR030918; PT_fungal_PKS.
DR   InterPro; IPR032088; SAT.
DR   InterPro; IPR016039; Thiolase-like.
DR   Pfam; PF00698; Acyl_transf_1; 1.
DR   Pfam; PF00109; ketoacyl-synt; 1.
DR   Pfam; PF02801; Ketoacyl-synt_C; 1.
DR   Pfam; PF00550; PP-binding; 1.
DR   Pfam; PF14765; PS-DH; 1.
DR   Pfam; PF16073; SAT; 1.
DR   SMART; SM00827; PKS_AT; 1.
DR   SMART; SM00825; PKS_KS; 1.
DR   SMART; SM00823; PKS_PP; 1.
DR   SUPFAM; SSF47336; SSF47336; 1.
DR   SUPFAM; SSF52151; SSF52151; 1.
DR   SUPFAM; SSF53901; SSF53901; 1.
DR   SUPFAM; SSF55048; SSF55048; 1.
DR   TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR   PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR   PROSITE; PS50075; CARRIER; 1.
PE   1: Evidence at protein level;
KW   Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW   Reference proteome; Transferase.
FT   CHAIN           1..1771
FT                   /note="Atrochrysone carboxylic acid synthase"
FT                   /id="PRO_0000437048"
FT   DOMAIN          1693..1770
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          38..269
FT                   /note="N-terminal acylcarrier protein transacylase domain
FT                   (SAT)"
FT                   /evidence="ECO:0000255"
FT   REGION          405..839
FT                   /note="Ketosynthase (KS) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          937..1257
FT                   /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          1322..1641
FT                   /note="Product template (PT) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          1668..1695
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        575
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT   MOD_RES         1730
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1771 AA;  194116 MW;  CA613F776D283D75 CRC64;
     MDFTPSTGTP GEFRRMKLTY FTNEFPSDDL PGLARQLHLH SKDRRHHILA RFLQDATLAI
     REEVAQLPPA LKDLLPPFES VLTFVEYPEM RKGPLCGSID GVLLSTVELA TFIGYFEEFP
     ETYDFESAHT YLAGLGIGLL SAAAVSLSRT LADIAYVGSE VVRMAFRLGV LVDNVSEQLQ
     PRELASHGTP DSWAYVLPNV TREAVQQELD VIHSGEGIPE TGKIFVSAFS QSSVTVSGPP
     SRLKDLFRTS DFFRDRRFFS LPVFGGLCHA KHIYTETHVQ QVVRTKPMDM LSARVLPRIP
     IFSPSSGSPF PAATATELFE GIISEILTQV IQWDNVIQGA LDQINILSPS EFQVLVFRIS
     LPIHDLMAAV NTELKGFQAT TKEIMPWVSH TAKDRIPREP SQSKIAIVGM SCRLPGGATN
     TEKFWDVLEQ GLDVYRTIPP DRFDVNTHYD PAGKRVNASH TPYGCFIEEP GLFDAPFFNM
     SPREAQQTDP MQRLALVTAY EALERAGYVP NRTPATNKHR IGTFYGQASD DYREVNTAQD
     VDTYFITGGC RAFGPGRINY FFKFWGPSYS IDTACSSSLA TVEAACTSLW NGSTDTAVVG
     GVNVLTNSDA FAGLSRGHFL SKIPGACKTW DCNADGYCRA DGVISLVMKR LEDAQADNDN
     ILGVILGAAT NHSADAVSIT HPHAGAQAHL FRDVLRNAGV DSHDVSYVEL HGTGTQAGDF
     EEMKSVTDVF APLTKRRSPN QPLYVGAVKA NVGHGEAVAG VTALLKVLLM LQKSVIPPHV
     GIKNSINPQI PKDLDKRNLH IPYEKQSWKS TPGKSRIAVV NNFSAAGGNT SVVLEEGPVT
     ELTGVDPRPS HVVAISAKSK VSLKGNLERF AAYIDTNPGV SLSHLSYTTM ARRHHHNHRL
     AAAVSDAEQL KKQLTSWMQS VESHRPISAT GPPPVAFAFT GQGASYKSMN VELFHTLPSF
     REQMMHLDAL AQQQGFPSFI PAIDGSHPQD HAHSQVVTQL ALTGTQIALA KYWMSLGVRP
     EVVVGHSLGE FAALHIAGVL SAGDTLFLVG RRAQLLEQHC VQGSYQMLAV RASVSQIEEI
     ADGRLYEVAC INGPKETVLS GTRQEIRNIA EHLMTKGYKC TALEVAFAGH SAQLDPILDT
     YEQIATKGAI FHPPNLPIIS PLLGKVIFDD KTVNATYMRR ASRETVNFHA ALETAQRIST
     VDDTTAWVEI GPHPVCMGFI RSTLQSTALT VPSLRRGEES WVTITRSLSS LHCAGVEVHW
     NEFHRPFEQA LRLLDLPTYS WNDKNYWIQY NGDWALTKGN TFYSSQQQNS AAVDELPSGP
     RTSTVQKIVE ESFDGRAARV VMQSDLMQSD LLEAAYGHKM NGCGVVTSSI HADVGFTLGQ
     YVYKKLNPNT KVPAMNMASL EVLKGLVANK NTDKPQRFQV TVTTTDINSR ILQLEWRNVH
     AHGPAEEPFA SAKIYYCDAS EWLLSWRPTL HLVQGRIQAL ERLAEAGIAN RFSGRMAYNL
     FANSLVDYAG KYRGMQSVVM HELEAFADVT LTVEKAGTWT VPPYFIDSVA HLAGFIMNVS
     DAIDNQKNFC VTPGWNSMRF AAPLVAGGRY RSYVKMIPTV EDDSVYLGDV YILQNDMIIG
     MVGGIKFRRY PRLLLNRFFS PSDDSTAKTA AGETPPAPTT TAATAITAAT STTSTTSTAS
     TGQPPKVDET SPVDSNSTAA RALALVAKEA GMEVTDLQDD AIFANLGVDS LMSLVIAEKF
     REELGVVVAG SLFLEYPTVG DLKSWLLEYY S