ID STCE_EMENI Reviewed; 263 AA.
AC Q00674; C8VDU5; Q5AV59;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 3.
DT 27-MAR-2024, entry version 113.
DE RecName: Full=Norsolorinic acid ketoreductase stcE {ECO:0000303|PubMed:8643646};
DE EC=1.1.1.349 {ECO:0000250|UniProtKB:Q00278};
DE AltName: Full=Short chain dehydrogenase stcE {ECO:0000305};
DE AltName: Full=Sterigmatocystin biosynthesis cluster protein E {ECO:0000303|PubMed:8643646};
GN Name=stcE {ECO:0000303|PubMed:8643646}; ORFNames=AN7821;
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: Short chain dehydrogenase; 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). 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 -!- CATALYTIC ACTIVITY:
CC Reaction=(1'S)-averantin + NADP(+) = H(+) + NADPH + norsolorinic acid;
CC Xref=Rhea:RHEA:35447, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:71533, ChEBI:CHEBI:77899;
CC EC=1.1.1.349; Evidence={ECO:0000250|UniProtKB:Q00278};
CC -!- PATHWAY: Mycotoxin biosynthesis; sterigmatocystin biosynthesis.
CC {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 -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAA61609.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; U34740; AAC49194.1; -; Genomic_DNA.
DR EMBL; AACD01000132; EAA61609.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BN001304; CBF80176.1; -; Genomic_DNA.
DR RefSeq; XP_681090.1; XM_675998.1.
DR AlphaFoldDB; Q00674; -.
DR SMR; Q00674; -.
DR BioGRID; 1950339; 1.
DR STRING; 227321.Q00674; -.
DR EnsemblFungi; CBF80176; CBF80176; ANIA_07821.
DR KEGG; ani:AN7821.2; -.
DR VEuPathDB; FungiDB:AN7821; -.
DR eggNOG; KOG1611; Eukaryota.
DR HOGENOM; CLU_010194_9_1_1; -.
DR InParanoid; Q00674; -.
DR OMA; NCTVIAA; -.
DR OrthoDB; 1703151at2759; -.
DR UniPathway; UPA00377; -.
DR Proteomes; UP000000560; Chromosome IV.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0140393; F:norsolorinic acid ketoreductase activity; IEA:RHEA.
DR GO; GO:0045461; P:sterigmatocystin biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd05325; carb_red_sniffer_like_SDR_c; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR PANTHER; PTHR43544; SHORT-CHAIN DEHYDROGENASE/REDUCTASE; 1.
DR PANTHER; PTHR43544:SF12; ZGC:65997; 1.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
PE 2: Evidence at transcript level;
KW NADP; Oxidoreductase; Reference proteome; Virulence.
FT CHAIN 1..263
FT /note="Norsolorinic acid ketoreductase stcE"
FT /id="PRO_0000054780"
FT ACT_SITE 177
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O93868"
FT ACT_SITE 181
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250|UniProtKB:O93868"
FT BINDING 29
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:L0E2Z4"
FT BINDING 76
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:L0E2Z4"
FT BINDING 105
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O93868"
FT BINDING 177
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O93868"
FT BINDING 181
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O93868"
FT BINDING 208
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O93868"
FT BINDING 210
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:L0E2Z4"
FT CONFLICT 23..31
FT /note="TGASRGLGR -> NRCQQG (in Ref. 1; AAC49194)"
FT /evidence="ECO:0000305"
FT CONFLICT 174
FT /note="L -> V (in Ref. 1; AAC49194)"
FT /evidence="ECO:0000305"
FT CONFLICT 215..216
FT /note="QA -> RS (in Ref. 1; AAC49194)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 263 AA; 28081 MW; BF201B693D5995E2 CRC64;
MPSAAVSVPE VPSSDRKTVY LVTGASRGLG RGLVQAFLLR PNSIVIAGLR NRTSQAGALD
ALPRGENSSL IAVQLDSGSK SDPADAVSIL QRDYGITHLD VVIANAAIAA NYGPASTMPL
EYLETHMQIN AYAALLLFQA TRVLLQAAKS PQFICVGAPI STITEMESCA RAPLTNYALS
KLAACYLVRK IHFENKWLVA YIVDPGHIQS DMGAQAARLF GRKEAPTTIE ESVAGICARM
TEADKNTTSG RFILFSDGSD VPW
//
