STCU_EMENI
ID STCU_EMENI Reviewed; 264 AA.
AC Q00791; C8VDS8; Q00726; Q5AV74;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Versicolorin reductase stcU {ECO:0000303|PubMed:8017929};
DE EC=1.3.1.- {ECO:0000305|PubMed:8017929};
DE AltName: Full=Sterigmatocystin biosynthesis cluster protein U {ECO:0000303|PubMed:8643646};
GN Name=stcU {ECO:0000303|PubMed:8643646};
GN Synonyms=verA {ECO:0000303|PubMed:8017929}; ORFNames=AN7806;
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, DISRUPTION
RP PHENOTYPE, AND PATHWAY.
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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], 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 [3]
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 [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.
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: Versicolorin reductase; 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:8017929, PubMed:8643646).
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:8017929, ECO:0000269|PubMed:8643646,
CC ECO:0000269|PubMed:8900026, ECO:0000269|PubMed:8962148,
CC ECO:0000269|PubMed:8999832, ECO:0000303|PubMed:24957370,
CC ECO:0000305|PubMed:8643646}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4S,8R)-2,13,16,20-tetrahydroxy-7,9-
CC dioxapentacyclo[10.8.0.0(3,10).0(4,8).0(14,19)]icosa-
CC 1(12),2,5,10,13,16,19-heptaen-18-one + H(+) + NADPH = (4S,8R,16R)-
CC 2,13,16,20-tetrahydroxy-7,9-
CC dioxapentacyclo[10.8.0.0(3,10).0(4,8).0(14,19)]icosa-
CC 1(12),2,5,10,13,19-hexaen-18-one + NADP(+); Xref=Rhea:RHEA:64296,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:150859, ChEBI:CHEBI:150860;
CC Evidence={ECO:0000305|PubMed:8017929};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64297;
CC Evidence={ECO:0000305|PubMed:8017929};
CC -!- PATHWAY: Mycotoxin biosynthesis; sterigmatocystin biosynthesis.
CC {ECO:0000269|PubMed:8017929, 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:8017929}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; L27825; AAA53572.1; -; Genomic_DNA.
DR EMBL; U34740; AAC49205.1; -; Genomic_DNA.
DR EMBL; AACD01000132; EAA61594.1; -; Genomic_DNA.
DR EMBL; BN001304; CBF80146.1; -; Genomic_DNA.
DR RefSeq; XP_681075.1; XM_675983.1.
DR AlphaFoldDB; Q00791; -.
DR SMR; Q00791; -.
DR STRING; 162425.CADANIAP00000947; -.
DR EnsemblFungi; CBF80146; CBF80146; ANIA_07806.
DR EnsemblFungi; EAA61594; EAA61594; AN7806.2.
DR GeneID; 2869435; -.
DR KEGG; ani:AN7806.2; -.
DR VEuPathDB; FungiDB:AN7806; -.
DR eggNOG; KOG0725; Eukaryota.
DR HOGENOM; CLU_010194_1_3_1; -.
DR InParanoid; Q00791; -.
DR OMA; ITGGRNW; -.
DR OrthoDB; 913128at2759; -.
DR UniPathway; UPA00377; -.
DR Proteomes; UP000000560; Chromosome IV.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0042469; F:versicolorin reductase activity; IMP:AspGD.
DR GO; GO:0045461; P:sterigmatocystin biosynthetic process; IMP:AspGD.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 2: Evidence at transcript level;
KW NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..264
FT /note="Versicolorin reductase stcU"
FT /id="PRO_0000054781"
FT ACT_SITE 160
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 15..39
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 16..44
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P16544"
FT BINDING 146
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 164
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P16544"
FT CONFLICT 34
FT /note="R -> P (in Ref. 1; AAA53572)"
FT /evidence="ECO:0000305"
FT CONFLICT 60..62
FT /note="GSD -> AQS (in Ref. 1; AAA53572)"
FT /evidence="ECO:0000305"
FT CONFLICT 60..62
FT /note="GSD -> AQT (in Ref. 2; AAC49205)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 264 AA; 28056 MW; B300687B7688B0A1 CRC64;
MSSSDNYRLD GKVALVTGAG RGIGAAIAVA LGQRGAKVVV NYANSREAAE KVVDEIKSNG
SDAISIQADV GDPDAVTKLM DQAVEHFGYL DIVSSNAGIV SFGHVKDVTP DEFDRVFRVN
TRGQFFVARE AYRHLREGGR IILTSSNTAS VKGVPRHAVY SGSKGAIDTF VRCLAIDCGD
KKITVNAVAP GAIKTDMFLS VSREYIPNGE TFTDEQVDEC AAWLSPLNRV GLPVDVARVV
SFLASDAAEW ISGKIIGVDG GAFR
