STCO_EMENI
ID STCO_EMENI Reviewed; 297 AA.
AC Q00710; C8VDT3; Q5AV69;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Averufin oxidase stcO {ECO:0000305|PubMed:8643646};
DE EC=1.-.-.- {ECO:0000305|PubMed:8643646};
DE AltName: Full=Sterigmatocystin biosynthesis cluster protein O {ECO:0000303|PubMed:8643646};
GN Name=stcO {ECO:0000303|PubMed:8643646}; ORFNames=AN7811;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, FUNCTION, AND PATHWAY.
RC STRAIN=FGSC 26;
RX PubMed=8643646; DOI=10.1073/pnas.93.4.1418;
RA Brown D.W., Yu J.-H., Kelkar H.S., Fernandes M., Nesbitt T.C., Keller N.P.,
RA Adams T.H., Leonard T.J.;
RT "Twenty-five coregulated transcripts define a sterigmatocystin gene cluster
RT in Aspergillus nidulans.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:1418-1422(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [4]
RP FUNCTION, AND INDUCTION.
RX PubMed=8017929; DOI=10.1128/aem.60.5.1444-1450.1994;
RA Keller N.P., Kantz N.J., Adams T.H.;
RT "Aspergillus nidulans verA is required for production of the mycotoxin
RT sterigmatocystin.";
RL Appl. Environ. Microbiol. 60:1444-1450(1994).
RN [5]
RP FUNCTION.
RX PubMed=7486998; DOI=10.1128/aem.61.10.3628-3632.1995;
RA Keller N.P., Segner S., Bhatnagar D., Adams T.H.;
RT "StcS, a putative P-450 monooxygenase, is required for the conversion of
RT versicolorin A to sterigmatocystin in Aspergillus nidulans.";
RL Appl. Environ. Microbiol. 61:3628-3632(1995).
RN [6]
RP FUNCTION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=7642507; DOI=10.1128/jb.177.16.4792-4800.1995;
RA Yu J.-H., Leonard T.J.;
RT "Sterigmatocystin biosynthesis in Aspergillus nidulans requires a novel
RT type I polyketide synthase.";
RL J. Bacteriol. 177:4792-4800(1995).
RN [7]
RP FUNCTION.
RX PubMed=8900026; DOI=10.1128/aem.62.11.4296-4298.1996;
RA Kelkar H.S., Keller N.P., Adams T.H.;
RT "Aspergillus nidulans stcP encodes an O-methyltransferase that is required
RT for sterigmatocystin biosynthesis.";
RL Appl. Environ. Microbiol. 62:4296-4298(1996).
RN [8]
RP FUNCTION.
RX PubMed=8962148; DOI=10.1073/pnas.93.25.14873;
RA Brown D.W., Adams T.H., Keller N.P.;
RT "Aspergillus has distinct fatty acid synthases for primary and secondary
RT metabolism.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:14873-14877(1996).
RN [9]
RP FUNCTION.
RX PubMed=8999832; DOI=10.1074/jbc.272.3.1589;
RA Kelkar H.S., Skloss T.W., Haw J.F., Keller N.P., Adams T.H.;
RT "Aspergillus nidulans stcL encodes a putative cytochrome P-450
RT monooxygenase required for bisfuran desaturation during
RT aflatoxin/sterigmatocystin biosynthesis.";
RL J. Biol. Chem. 272:1589-1594(1997).
RN [10]
RP INDUCTION.
RX PubMed=9680223; DOI=10.1046/j.1365-2958.1998.00907.x;
RA Fernandes M., Keller N.P., Adams T.H.;
RT "Sequence-specific binding by Aspergillus nidulans aflR, a C6 zinc cluster
RT protein regulating mycotoxin biosynthesis.";
RL Mol. Microbiol. 28:1355-1365(1998).
RN [11]
RP FUNCTION.
RX PubMed=10618248; DOI=10.1128/aem.66.1.359-362.2000;
RA Keller N.P., Watanabe C.M., Kelkar H.S., Adams T.H., Townsend C.A.;
RT "Requirement of monooxygenase-mediated steps for sterigmatocystin
RT biosynthesis by Aspergillus nidulans.";
RL Appl. Environ. Microbiol. 66:359-362(2000).
RN [12]
RP REVIEW ON STERIGMATOCYSTIN BIOSYNTHESIS.
RX PubMed=24957370; DOI=10.3390/metabo2010100;
RA Klejnstrup M.L., Frandsen R.J., Holm D.K., Nielsen M.T., Mortensen U.H.,
RA Larsen T.O., Nielsen J.B.;
RT "Genetics of polyketide metabolism in Aspergillus nidulans.";
RL Metabolites 2:100-133(2012).
CC -!- FUNCTION: Averufin oxidase; part of the gene cluster that mediates the
CC biosynthesis of sterigmatocystin (ST), a polyketide-derived
CC furanocoumarin which is part of the most toxic and carcinogenic
CC compounds among the known mycotoxins (PubMed:8643646). The first step
CC in the biosynthesis of sterigmatocystin is the production of hexanoate
CC by the fatty acid synthase (FAS) units stcJ and stcK (PubMed:8962148).
CC The polyketide backbone is assembled by the non-reducing polyketide
CC synthase stcA by condensation of the starter hexanoyl-CoA and 7
CC malonyl-CoA extender units followed by cyclization and release of
CC norsolorinic acid (By similarity). Norsolorinic acid is the first
CC stable intermediate in the biosynthesis of sterigmatocystin and is
CC converted into averantin (AVN) by the ketoreductase stcE which reduces
CC the hexanoate ketone to an alcohol (PubMed:8643646) (Probable).
CC Averantin is then oxidized into 5'-hydroxyaverantin (HAVN) by the
CC cytochrome P450 monooxygenase stcF (PubMed:10618248). 5'-
CC hydroxyaverantin is further converted to 5'-oxyaverantin (OAVN) by the
CC 5'-hydroxyaverantin dehydrogenase stcG (PubMed:24957370). The next step
CC is the conversion of OAVN into averufin (AVF) which is catalyzed by a
CC yet to be identified enzyme (PubMed:24957370). The cytochrome P450
CC monoxygenase stcB and the flavin-binding monooxygenase stcW are both
CC required for the conversion of averufin to 1-hydroxyversicolorone
CC (PubMed:10618248). The esterase stcI probably catalyzes the formation
CC of versiconal hemiacetal acetate from 1-hydroxyversicolorone
CC (PubMed:24957370). The oxydoreductase stcN then probably catalyzes the
CC biosynthetic step from versiconal to versicolorin B (VERB)
CC (PubMed:24957370). The next step is performed by the versicolorin B
CC desaturase stcL to produce versicolorin A (VERA) (PubMed:8999832). The
CC ketoreductase stcU and the cytochrome P450 monooxygenase stcS are
CC involved in the conversion of versicolorin A to
CC demethylsterigmatocystin (PubMed:7486998). The Baeyer-Villiger oxidas
CC stcQ and the reductase stcR might be involved in the biosynthetic step
CC from versicolorin A to demethylsterigmatocystin (PubMed:24957370). The
CC final step in the biosynthesis of sterigmatocystin is the methylation
CC of demethylsterigmatocystin catalyzed by the methyltransferase stcP
CC (PubMed:8900026). {ECO:0000250|UniProtKB:Q12053,
CC ECO:0000269|PubMed:10618248, ECO:0000269|PubMed:7486998,
CC ECO:0000269|PubMed:8643646, ECO:0000269|PubMed:8900026,
CC ECO:0000269|PubMed:8962148, ECO:0000269|PubMed:8999832,
CC ECO:0000303|PubMed:24957370, ECO:0000305|PubMed:8643646}.
CC -!- PATHWAY: Mycotoxin biosynthesis; sterigmatocystin biosynthesis.
CC {ECO:0000269|PubMed:8643646}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: The genes forming the sterigmatocystin biosynthesis cluster
CC are co-regulated and induced on oatmeal porridge or the fungal isolates
CC were grown either on oatmeal porridge or in YEC medium (0.2% yeast
CC extract, 5.0% corn steep liquor) (PubMed:8643646, PubMed:8017929).
CC Expression is positively regulated by the cluster-specific
CC transcription factor aflR that binds the palindromic sequence 5'-
CC TCG(N5)CGA-3'found in the promoter (PubMed:9680223).
CC {ECO:0000269|PubMed:8017929, ECO:0000269|PubMed:8643646,
CC ECO:0000269|PubMed:9680223}.
CC -!- SIMILARITY: Belongs to the avfA family. {ECO:0000305}.
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DR EMBL; U34740; AAC49201.1; -; Genomic_DNA.
DR EMBL; AACD01000132; EAA61599.1; -; Genomic_DNA.
DR EMBL; BN001304; CBF80154.1; -; Genomic_DNA.
DR RefSeq; XP_681080.1; XM_675988.1.
DR AlphaFoldDB; Q00710; -.
DR EnsemblFungi; CBF80154; CBF80154; ANIA_07811.
DR EnsemblFungi; EAA61599; EAA61599; AN7811.2.
DR GeneID; 2869446; -.
DR KEGG; ani:AN7811.2; -.
DR VEuPathDB; FungiDB:AN7811; -.
DR eggNOG; ENOG502SM0C; Eukaryota.
DR HOGENOM; CLU_090039_0_0_1; -.
DR InParanoid; Q00710; -.
DR OMA; GAAMCEI; -.
DR OrthoDB; 1166292at2759; -.
DR UniPathway; UPA00377; -.
DR Proteomes; UP000000560; Chromosome IV.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004074; F:biliverdin reductase (NAD(P)+) activity; IBA:GO_Central.
DR GO; GO:0016646; F:oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0042602; F:riboflavin reductase (NADPH) activity; IBA:GO_Central.
DR GO; GO:0044281; P:small molecule metabolic process; IEA:UniProt.
DR GO; GO:0045461; P:sterigmatocystin biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF13460; NAD_binding_10; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW Membrane; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..297
FT /note="Averufin oxidase stcO"
FT /id="PRO_0000072258"
FT TRANSMEM 277..297
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 297 AA; 31719 MW; 9C027B5531212802 CRC64;
MPSYALLGAT GATGSSVLRH LLYSGSSSDL TVNVLVRSKS KLLAAFPSLD KPRPSVTSSI
PTIRIFEGDS TNPDVLCAVL QDASLVFMCV AQNGSPMGTT LVQNTAAALI EARRRQAQPR
GELTVIQLRS ASLNPVLAVQ VPRFVHRVVC FCLAAGYADL RRACVLYEAA ATEGLLQYVL
VDPPTLHDAR GTQTTGYRLI DTTDMKDKEN QRQAICLSYA DLGVAMCEIA SRADELHGQG
VGVTATGPVR QTWAVLAGFL LEGGLGHLDY RYGRENVVVL GVCILLLLGG LLYSIKA
