OTAA_ASPNC
ID OTAA_ASPNC Reviewed; 2550 AA.
AC A2R6H1;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 2.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Highly reducing polyketide synthase otaA {ECO:0000303|PubMed:27959549};
DE EC=2.3.1.- {ECO:0000269|PubMed:27959549};
DE AltName: Full=Ochratoxin biosynthesis cluster protein 1 {ECO:0000303|PubMed:27667988};
DE AltName: Full=Ochratoxin biosynthesis cluster protein A {ECO:0000303|PubMed:33391201};
GN Name=otaA {ECO:0000303|PubMed:33391201};
GN Synonyms=ota1 {ECO:0000303|PubMed:27667988}; ORFNames=An15g07920;
OS Aspergillus niger (strain CBS 513.88 / FGSC A1513).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=425011;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 513.88 / FGSC A1513 / ATCC MYA-4892;
RX PubMed=17259976; DOI=10.1038/nbt1282;
RA Pel H.J., de Winde J.H., Archer D.B., Dyer P.S., Hofmann G., Schaap P.J.,
RA Turner G., de Vries R.P., Albang R., Albermann K., Andersen M.R.,
RA Bendtsen J.D., Benen J.A.E., van den Berg M., Breestraat S., Caddick M.X.,
RA Contreras R., Cornell M., Coutinho P.M., Danchin E.G.J., Debets A.J.M.,
RA Dekker P., van Dijck P.W.M., van Dijk A., Dijkhuizen L., Driessen A.J.M.,
RA d'Enfert C., Geysens S., Goosen C., Groot G.S.P., de Groot P.W.J.,
RA Guillemette T., Henrissat B., Herweijer M., van den Hombergh J.P.T.W.,
RA van den Hondel C.A.M.J.J., van der Heijden R.T.J.M., van der Kaaij R.M.,
RA Klis F.M., Kools H.J., Kubicek C.P., van Kuyk P.A., Lauber J., Lu X.,
RA van der Maarel M.J.E.C., Meulenberg R., Menke H., Mortimer M.A.,
RA Nielsen J., Oliver S.G., Olsthoorn M., Pal K., van Peij N.N.M.E.,
RA Ram A.F.J., Rinas U., Roubos J.A., Sagt C.M.J., Schmoll M., Sun J.,
RA Ussery D., Varga J., Vervecken W., van de Vondervoort P.J.J., Wedler H.,
RA Woesten H.A.B., Zeng A.-P., van Ooyen A.J.J., Visser J., Stam H.;
RT "Genome sequencing and analysis of the versatile cell factory Aspergillus
RT niger CBS 513.88.";
RL Nat. Biotechnol. 25:221-231(2007).
RN [2]
RP IDENTIFICATION, AND DOMAIN.
RX PubMed=22341916; DOI=10.1016/j.ijfoodmicro.2012.01.020;
RA Ferracin L.M., Fier C.B., Vieira M.L., Monteiro-Vitorello C.B.,
RA Varani A.M., Rossi M.M., Mueller-Santos M., Taniwaki M.H.,
RA Thie Iamanaka B., Fungaro M.H.;
RT "Strain-specific polyketide synthase genes of Aspergillus niger.";
RL Int. J. Food Microbiol. 155:137-145(2012).
RN [3]
RP FUNCTION.
RX PubMed=27667988; DOI=10.3389/fmicb.2016.01412;
RA Susca A., Proctor R.H., Morelli M., Haidukowski M., Gallo A.,
RA Logrieco A.F., Moretti A.;
RT "Variation in fumonisin and ochratoxin production associated with
RT differences in biosynthetic gene content in Aspergillus niger and A.
RT welwitschiae isolates from multiple crop and geographic origins.";
RL Front. Microbiol. 7:1412-1412(2016).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, INDUCTION, AND PATHWAY.
RX PubMed=27959549; DOI=10.1021/acs.jafc.6b03907;
RA Zhang J., Zhu L., Chen H., Li M., Zhu X., Gao Q., Wang D., Zhang Y.;
RT "A polyketide synthase encoded by the gene An15g07920 is involved in the
RT biosynthesis of ochratoxin A in Aspergillus niger.";
RL J. Agric. Food Chem. 64:9680-9688(2016).
RN [5]
RP NOMENCLATURE, AND FUNCTION.
RX PubMed=33391201; DOI=10.3389/fmicb.2020.581309;
RA Ferrara M., Gallo A., Perrone G., Magista D., Baker S.E.;
RT "Comparative genomic analysis of ochratoxin A biosynthetic cluster in
RT producing fungi: new evidence of a cyclase gene involvement.";
RL Front. Microbiol. 11:581309-581309(2020).
RN [6]
RP INDUCTION.
RX PubMed=35143724; DOI=10.1021/acs.jafc.1c08160;
RA Zhang J., Li L., Yang Y., Zhao C., Hu J., Xue X., Gao Q., Wang D.,
RA Zhuang Z., Zhang Y.;
RT "Deletion and overexpression of the AnOTAbzip gene, a positive regulator of
RT ochratoxin A biosynthesis in Aspergillus niger.";
RL J. Agric. Food Chem. 70:2169-2178(2022).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of ochratoxin A (OTA), a mycotoxin
CC composed of a chlorinated type I polyketide dihydroisocoumarin moiety
CC linked to L-phenylalanine, and demonstrated to have nephrotoxic,
CC immunotoxic, genotoxic, neurotoxic, and teratogenic properties
CC (PubMed:27667988, PubMed:27959549). OtaA catalyzes the condensation of
CC one acetate and 4 malonate units to form the isocoumarin group
CC (PubMed:27959549). The pathway begins with the highly reducing
CC polyketide synthase otaA that catalyzes the formation of the
CC isocoumarin group during the initial stages of biosynthesis, starting
CC from one acetate and 4 malonate units, to originate the characteristic
CC pentaketide skeleton 7-methylmellein (7-MM) of the OTA molecule. The
CC newly identified cyclase otaY might be involved in the polyketide
CC cyclization reaction during the initial steps of the OTA biosynthesis.
CC 7-MM is then oxidized into 7-carboxymellein (also called ochratoxin
CC beta) by the cytochrome P450 monooxygenase otaC. The NRPS encoded by
CC the otaB gene is involved in the linking of phenylalanine to the
CC dihydroisocoumarin ring. The reaction catalyzed by NRPS results in the
CC production of ochratoxin B (OTB), which is the non-chlorinated analog
CC of OTA and which subsequently serves as the substrate of the halogenase
CC otaD for chlorination activity to form the final molecular structure of
CC OTA, containing a chlorine atom in the C-5 position of the molecule
CC (PubMed:27667988, PubMed:33391201) (Probable).
CC {ECO:0000269|PubMed:27667988, ECO:0000269|PubMed:27959549,
CC ECO:0000305|PubMed:27667988, ECO:0000305|PubMed:33391201}.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000255};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000255};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:27959549}.
CC -!- INDUCTION: Expression reaches reached its maximum level before
CC ochratoxin A accumulation reaches its highest level (PubMed:27959549).
CC Expression is positively regulated by the ochratoxin cluster
CC transcription factor otaR1, probably via its binding to the conserved
CC 5'-ACGT-3' bZIP binding motifs found in multiple copies (3 to 4) in the
CC promoters of the OTA biosynthetic genes (PubMed:35143724).
CC {ECO:0000269|PubMed:27959549, ECO:0000269|PubMed:35143724}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; a methyltransferase
CC (CMeT) domain responsible for the incorporation of methyl groups; an
CC enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and
CC an acyl-carrier protein (ACP) that serves as the tether of the growing
CC and completed polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:22341916}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of ochratoxin alpha,
CC ochratoxin beta, and ochratoxin A (PubMed:27959549).
CC {ECO:0000269|PubMed:27959549}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAK42679.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AM270352; CAK42679.1; ALT_SEQ; Genomic_DNA.
DR AlphaFoldDB; A2R6H1; -.
DR SMR; A2R6H1; -.
DR PaxDb; A2R6H1; -.
DR EnsemblFungi; CAK42679; CAK42679; An15g07920.
DR HOGENOM; CLU_000022_31_0_1; -.
DR Proteomes; UP000006706; Chromosome 3R.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:1900818; P:ochratoxin A biosynthetic process; IMP:GO_Central.
DR GO; GO:0019748; P:secondary metabolic process; NAS:AspGD.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 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; IPR011032; GroES-like_sf.
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; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 2: Evidence at transcript level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2550
FT /note="Highly reducing polyketide synthase otaA"
FT /id="PRO_0000440589"
FT DOMAIN 2454..2531
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 12..434
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22341916"
FT REGION 572..894
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22341916"
FT REGION 959..1252
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22341916"
FT REGION 1433..1612
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22341916"
FT REGION 1859..1919
FT /note="Enoyl reductase (ER) (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22341916"
FT REGION 2166..2345
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22341916"
FT ACT_SITE 182
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT BINDING 1420
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 1442
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT MOD_RES 2491
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2550 AA; 277318 MW; F57292F2476EFE23 CRC64;
MSSAPIPQSE PLAIIGLACK YANGIDSPEA LYEQVMAARC MHGAMPSNRM DASFYYHPTS
EATGTSYSKG GYFLNCDLNA FDSPFFQLSE IDVMAMDPQQ KMLLENVYHA LENAGIPLKN
AISSPTSVFV GCSNNDHLAL ANSDLLLSLK GKGTGTSPSI LANRVSWFYD FQGTSQTIDT
ACSSSLVAFH QGCMDVRAGK SAMSIISGIN LIEHPGPTLY LSSLGVLSPD GKSMSFDARA
NGYGRGEGVG TVIVKPLQAA LRDGNRIRAI VRSTGSNQDG RTPGITVPNP SAQERLIHDV
YRVADLDPRR TGYVEAHGTG TQVGDPLEVQ AILAALGVAR DSPLYVGSVK SVLGHLEGGA
GLAGLISATL AVESKMIPPV AGLQSLNPKI PQRDDLKFAR EATPWPRWDV RRASINSFGF
GGTNAHAVVE DVEGFFADLF GQYIPGALPA PEVDTSLETT PMLSKPLMSG NASNQSVQSW
STSRLFVISA FDEAGIQRNT SALAEYLDSK STTADTDGED RLLNNLCHTL NEKRTRFDWR
SYHVADSIAS LRESLQHSRA IRQSSAPKPI RFVFTGQGAN WAGMACDMLK YPLFRRRIQE
AAAYLRELGS GWDLFERMTS KAGELDEPTF AQSSCVAVQV ALVDLLASWK VVPETVVGHS
SGEIAAAYCA GHISRQAAWK VAFCRGKVCA RRTDGQGRML AAAMPVHQLE RVVARVNKGQ
PTSVKIGCYN SPRNLTLTGR YDDILRLKLE LDDVGALNRM LPVKVAYHSD YMQDAAPEYL
SLLGEILDGG DTIHKDASIQ MISSVTGQPV PAGDVQQASY WVKNLVSPVR FCTALLASME
FPGTTGKRED TLIEIGPHST LRSAIKESFA EVPEYQSVQY GSLLKRYETN GSTILHTLGM
MFCSGHEISL AAINDRRVGT RKIPMLLTGL PGYAFDHSRS VRGTSRRIEQ VKFPTYNRHE
LLGVPVEDSN PYEQRWRNVL RPDDLPWLRM NRMKGQIHFP GVAYILMATE ALQQRVARTM
TIPRVRIANM SILAPLQVPD SPSGVEIQVS IYPTNVRANG ATDWATFRII SYDTAEKTWV
EHCVGSVRAE TGPPDLCVNT ALRKQCAEPV DIAQMYHGFT AAGMDFGENL RNIQAMKVSP
DRTACTATIT APSIAPQAHD QYPLHPCSFE SILHALLYLC EASQSPMVTN YIEEVVIVNP
NDTGAREFES FARRQRTSAT TWTCDVSITT NVGDQDIQIK GLDLVQLPAN NDDAVDAESF
YTVNWRPDVK LLASADALHN SAPVDAAQHL PTFDEHEGYQ LASAIFLQEA KEYVTRTGLP
PLPTHHQAFM DWMEEEYQSI NNGTTPLLDK SLLDGIRADP DRRKSLLDRV ARQSARGELL
VRVGTRMIDI LEQKIDCLEV MFGPDNLMER TYEEGLPGQI APAVAGYLHC LAHAQTGIKI
LEVGAGTGSA TKVMLDSLRP TEAQDGGGLV SSVSSYDFTD ISAAFFEKAR ARFHDWADIL
RPKLLNIEQD PAAQGFELGS YDLVIATHVL HATADLNVSL KNIRALLKEG GDLIVIENIQ
PKFMCSQLPF GLLPGWWRSV EPYRKTNPLI LKEHWTEELQ NAGLRPRLII NDTDDGINEM
SAFVASPMPK VLDGSQPCSI IYSSTYPGQQ QLALEVADRL PRSCTAAVVD LADISLDHSD
TVGIVLVGCQ GLDLSELTSS EYDRVKFILT SFQKLLWVTC DPTDVPKSAL ATGLVRSTRW
EREHDNVNII LLSVSLSRPT PLTISSEIVR LCENAFISCK RVPPNSEYRI EGSNGVLLTN
RLFPAAGINE CIGLGSRPRS RQVPLGTVDH PIKLTSIGSQ QPNGFHFIED PQAHEPLDPD
EVKIRIHAAG LDEEDADQLS RLIPGHGFGD QGSGTVVEIG HGVQGIQVGD QVMALRTGPS
CALQTFFRTH SATVAKIPDG IRLSDAAALP LPWVTAYHSL VTVARLDSQE KVLIHPAIGA
TGQAAVQVAS MLGATVYATV ETDAQRQTLA EYGVEESHIL DSASVEKQFG TQTSTQGVDV
LLNLRRDGLE FLHLSCLSPF GRLVDISGSR AFPSQVNSPS NQSYYRVNMR ELSQLKPESI
RQTLRTVAQL LASPTIRPVA PFRVGYSQLQ RVLSEIRRGS RGPWVIQPLP NDPIPPLGSH
QFDPSASYLL IGGFGGLGRS VARWMHHRGA KHFIFFSRSG ASSAAARELC ADLRAAGCAV
SDMICDTTDA QAVAKAMAQC EASMPPIRGC LQASMVLEDS MLSNMDHTRF LGAITPKVQG
TINVASALAP IKSNLDFFVM LSSSAGIVGN RGQANYAAAN TFLDAFAGQL VTQGYPATSV
SLGSVLSVGW VAENQHKLRI AFAFGALSED LLLSILEYHM DPAWGAAQSI QTCHTVVGVR
SARDFQRQSI PLPGFMAHPL FSPLLAIAGR SQTAEQAAEA PVSQGLREAS SMEAAVEVVT
RAIVHKLARI MALSVQEIDP QRSLGSYGVD SLVTVDLKAW FQREVGVSIG SGELLGEMAM
TQLAQQAADA SQFLPAELRG KLRKNTDIHV