STCS_EMENI
ID STCS_EMENI Reviewed; 488 AA.
AC Q00714; C8VDT0; Q00803; Q5AV72;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 26-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Cytochrome P450 monooxygenase stcS {ECO:0000303|PubMed:8643646};
DE EC=1.14.-.- {ECO:0000305|PubMed:7486998};
DE AltName: Full=Cytochrome P450 59;
DE AltName: Full=Sterigmatocystin biosynthesis cluster protein S {ECO:0000303|PubMed:7486998};
GN Name=stcS {ECO:0000303|PubMed:8643646}; Synonyms=cyp59, cyp59A1, verB;
GN ORFNames=AN7808;
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 PRELIMINARY PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND
RP INDUCTION.
RC STRAIN=FGSC 26;
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 [4]
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 [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
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: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of sterigmatocystin (ST), a polyketide-
CC derived furanocoumarin which is part of the most toxic and carcinogenic
CC compounds among the known mycotoxins (PubMed:8643646, PubMed:7486998).
CC The first step in the biosynthesis of sterigmatocystin is the
CC production of hexanoate by the fatty acid synthase (FAS) units stcJ and
CC stcK (PubMed:8962148). The polyketide backbone is assembled by the non-
CC reducing polyketide synthase stcA by condensation of the starter
CC hexanoyl-CoA and 7 malonyl-CoA extender units followed by cyclization
CC and release of norsolorinic acid (By similarity). Norsolorinic acid is
CC the first stable intermediate in the biosynthesis of sterigmatocystin
CC and is converted into averantin (AVN) by the ketoreductase stcE which
CC reduces 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 -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis; sterigmatocystin biosynthesis.
CC {ECO:0000269|PubMed:7486998, ECO:0000269|PubMed:8643646}.
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 -!- DISRUPTION PHENOTYPE: Impairs the production of sterigmatocystin and
CC leads to the accumulation of versicolorin A.
CC {ECO:0000269|PubMed:7486998}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA53574.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAC49203.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=EAA61596.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; U34740; AAC49203.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AACD01000132; EAA61596.1; ALT_SEQ; Genomic_DNA.
DR EMBL; L27825; AAA53574.1; ALT_FRAME; Genomic_DNA.
DR EMBL; BN001304; CBF80149.1; -; Genomic_DNA.
DR RefSeq; XP_681077.1; XM_675985.1.
DR AlphaFoldDB; Q00714; -.
DR SMR; Q00714; -.
DR STRING; 162425.CADANIAP00000949; -.
DR EnsemblFungi; CBF80149; CBF80149; ANIA_07808.
DR EnsemblFungi; EAA61596; EAA61596; AN7808.2.
DR GeneID; 2869532; -.
DR KEGG; ani:AN7808.2; -.
DR VEuPathDB; FungiDB:AN7808; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_020492_1_0_1; -.
DR InParanoid; Q00714; -.
DR OMA; FYLNLWP; -.
DR OrthoDB; 1247045at2759; -.
DR BioCyc; MetaCyc:MON-21285; -.
DR UniPathway; UPA00377; -.
DR Proteomes; UP000000560; Chromosome IV.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0042469; F:versicolorin reductase activity; IMP:AspGD.
DR GO; GO:0010914; P:positive regulation of sterigmatocystin biosynthetic process; IMP:AspGD.
DR GO; GO:0045461; P:sterigmatocystin biosynthetic process; IMP:AspGD.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 2: Evidence at transcript level;
KW Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..488
FT /note="Cytochrome P450 monooxygenase stcS"
FT /id="PRO_0000052046"
FT BINDING 417
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CONFLICT 75..77
FT /note="NIL -> PLV (in Ref. 3; AAA53574)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="R -> G (in Ref. 1; AAC49203 and 3; AAA53574)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 488 AA; 55353 MW; D003B55A77B3D037 CRC64;
MPSFSLLTGH FGALKQTIDG MPPNATLHSI MLKLSQKFRS GMFYINMWPF SGTWLVVATP
SGAAQIQSLN LSKPNILRRP LETITGGPSL MSMHGETWKR WRALFNPGFN PNYLIGLAPL
IADEVVVFCE QLRQKARTGT VFQLEPLTLR LTVDTICSVT LDSQLHHQTQ DHPLASALQR
QIEWASFGTT FNPFKRYLTV RPLVMWYNNR LMNRFIDQEV DRAYREQSGR QSKSVISLAL
RDYMKEKDGS LEDFKRRVAP QLRVFLFAGR DTTSSTLLYA FYLLSRHPEA LAKVRLEHDQ
VFGPYHQQVH EKIHQDAKLL NQLPYTTAVL KETLRLFPPS ASMREGRPGV EITDDNGQVY
PTAGCNVWTL TVALHHNSAH WAEAESFIPE RWLVGSDHPL YPAKGAWRAF EFGPRSCIGQ
TLAMLELRVA LAMTLREFDI APAYDKWDHI YPNDAVKEFN GHRAYQAEKG GGGAHPADGM
PCLVTFRV
