OTAA_ASPC5
ID OTAA_ASPC5 Reviewed; 2541 AA.
AC A0A1R3RGK0;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2017, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=Highly reducing polyketide synthase otaA {ECO:0000303|PubMed:30054361};
DE EC=2.3.1.- {ECO:0000269|PubMed:24699234};
DE AltName: Full=Ochratoxin A biosynthesis cluster protein A {ECO:0000303|PubMed:30054361};
GN Name=otaA {ECO:0000303|PubMed:30054361};
GN Synonyms=OTApks {ECO:0000303|PubMed:24699234}; ORFNames=ASPCADRAFT_173482;
OS Aspergillus carbonarius (strain ITEM 5010).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=602072;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ITEM 5010;
RX PubMed=28196534; DOI=10.1186/s13059-017-1151-0;
RA de Vries R.P., Riley R., Wiebenga A., Aguilar-Osorio G., Amillis S.,
RA Uchima C.A., Anderluh G., Asadollahi M., Askin M., Barry K., Battaglia E.,
RA Bayram O., Benocci T., Braus-Stromeyer S.A., Caldana C., Canovas D.,
RA Cerqueira G.C., Chen F., Chen W., Choi C., Clum A., Dos Santos R.A.,
RA Damasio A.R., Diallinas G., Emri T., Fekete E., Flipphi M., Freyberg S.,
RA Gallo A., Gournas C., Habgood R., Hainaut M., Harispe M.L., Henrissat B.,
RA Hilden K.S., Hope R., Hossain A., Karabika E., Karaffa L., Karanyi Z.,
RA Krasevec N., Kuo A., Kusch H., LaButti K., Lagendijk E.L., Lapidus A.,
RA Levasseur A., Lindquist E., Lipzen A., Logrieco A.F., MacCabe A.,
RA Maekelae M.R., Malavazi I., Melin P., Meyer V., Mielnichuk N., Miskei M.,
RA Molnar A.P., Mule G., Ngan C.Y., Orejas M., Orosz E., Ouedraogo J.P.,
RA Overkamp K.M., Park H.-S., Perrone G., Piumi F., Punt P.J., Ram A.F.,
RA Ramon A., Rauscher S., Record E., Riano-Pachon D.M., Robert V., Roehrig J.,
RA Ruller R., Salamov A., Salih N.S., Samson R.A., Sandor E., Sanguinetti M.,
RA Schuetze T., Sepcic K., Shelest E., Sherlock G., Sophianopoulou V.,
RA Squina F.M., Sun H., Susca A., Todd R.B., Tsang A., Unkles S.E.,
RA van de Wiele N., van Rossen-Uffink D., Oliveira J.V., Vesth T.C.,
RA Visser J., Yu J.-H., Zhou M., Andersen M.R., Archer D.B., Baker S.E.,
RA Benoit I., Brakhage A.A., Braus G.H., Fischer R., Frisvad J.C.,
RA Goldman G.H., Houbraken J., Oakley B., Pocsi I., Scazzocchio C.,
RA Seiboth B., vanKuyk P.A., Wortman J., Dyer P.S., Grigoriev I.V.;
RT "Comparative genomics reveals high biological diversity and specific
RT adaptations in the industrially and medically important fungal genus
RT Aspergillus.";
RL Genome Biol. 18:RESEARCH28.1-RESEARCH28.45(2017).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, DOMAIN, AND PATHWAY.
RX PubMed=24699234; DOI=10.1016/j.ijfoodmicro.2014.03.013;
RA Gallo A., Knox B.P., Bruno K.S., Solfrizzo M., Baker S.E., Perrone G.;
RT "Identification and characterization of the polyketide synthase involved in
RT ochratoxin A biosynthesis in Aspergillus carbonarius.";
RL Int. J. Food Microbiol. 179:10-17(2014).
RN [3]
RP INDUCTION.
RX PubMed=27548221; DOI=10.3390/toxins8080242;
RA El Khoury R., Atoui A., Verheecke C., Maroun R., El Khoury A., Mathieu F.;
RT "Essential oils modulate gene expression and ochratoxin A production in
RT Aspergillus carbonarius.";
RL Toxins 8:0-0(2016).
RN [4]
RP FUNCTION, INDUCTION, AND PATHWAY.
RX PubMed=30054361; DOI=10.1128/aem.01009-18;
RA Wang Y., Wang L., Wu F., Liu F., Wang Q., Zhang X., Selvaraj J.N., Zhao Y.,
RA Xing F., Yin W.B., Liu Y.;
RT "A consensus ochratoxin A biosynthetic pathway: insights from the genome
RT sequence of Aspergillus ochraceus and a comparative genomic analysis.";
RL Appl. Environ. Microbiol. 84:0-0(2018).
RN [5]
RP 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=33540740; DOI=10.3390/toxins13020111;
RA Gerin D., Garrapa F., Ballester A.R., Gonzalez-Candelas L.,
RA De Miccolis Angelini R.M., Faretra F., Pollastro S.;
RT "Functional role of Aspergillus carbonarius AcOTAbZIP gene, a bZIP
RT transcription factor within the OTA gene cluster.";
RL Toxins 13:0-0(2021).
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:24699234, PubMed:30054361). OtaA catalyzes the condensation of
CC one acetate and 4 malonate units to form the isocoumarin group
CC (PubMed:24699234). 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:33391201) (Probable). {ECO:0000269|PubMed:24699234,
CC ECO:0000269|PubMed:30054361, 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:24699234,
CC ECO:0000269|PubMed:30054361}.
CC -!- INDUCTION: Expression is down-regulated in the presence of fennel,
CC cardamom, chamomile, celery, anise and rosemary essential oils
CC (PubMed:27548221). Expression is positively regulated by the cluster-
CC specific transcription factor otaR1 (PubMed:30054361, PubMed:33540740).
CC Expression is also modulated by a second regulator, otaR2, which is
CC adjacent to the biosynthetic gene cluster (PubMed:30054361).
CC {ECO:0000269|PubMed:27548221, ECO:0000269|PubMed:30054361,
CC ECO:0000269|PubMed:33540740}.
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:24699234}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of ochratoxin A and its
CC degradation derivative ochratoxin alpha. {ECO:0000269|PubMed:24699234,
CC ECO:0000269|PubMed:30054361}.
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DR EMBL; KV907504; OOF93599.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1R3RGK0; -.
DR SMR; A0A1R3RGK0; -.
DR STRING; 602072.A0A1R3RGK0; -.
DR EnsemblFungi; OOF93599; OOF93599; ASPCADRAFT_173482.
DR VEuPathDB; FungiDB:ASPCADRAFT_173482; -.
DR OMA; KMRGGEF; -.
DR OrthoDB; 19161at2759; -.
DR BioCyc; MetaCyc:MON-21059; -.
DR Proteomes; UP000188318; Unassembled WGS sequence.
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 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; IPR013154; ADH_N.
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; PF08240; ADH_N; 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..2541
FT /note="Highly reducing polyketide synthase otaA"
FT /id="PRO_0000440588"
FT DOMAIN 2453..2530
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:24699234"
FT REGION 571..888
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:24699234"
FT REGION 957..1250
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:24699234"
FT REGION 1433..1605
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:24699234"
FT REGION 1857..1919
FT /note="Enoyl reductase (ER) (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:24699234"
FT REGION 2165..2344
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:24699234"
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 2490
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2541 AA; 274798 MW; F2ACF09BA03616CF CRC64;
MTFTSHPQSE PLAIIGLACK YANDINSPLD LYQQVMAARS MHGPMPPSRM DAAFYYHPSS
EATGTTYAKG GYFLQSDLNA FDSPFFQLSE IDVLAMDPQQ KMLLENVYHA LENAGIPLKD
AVSSSTSVFV GCSNNDHLAL ANADLLLALK GKGTGTSPSI LANRISWFYD FQGTSQTIDT
ACSSSLVAFH QGCMDVRAGK STMSIISGVN LMEHPAPTMY LSSLGVLSPD GRSMSFDARA
NGYGRGEGLG TVIIKPLTAA LRDGNRIRAI VRSTGSNQDG RTPGITVPSP TAQERLIREV
YKAADLDPSR TGYVEAHGTG TPVGDPLEVQ AISAALGMSR DSPLYVGSVK SVVGHLEGGA
GMAGLISATM AVESKTIPPV AGLQTLNPRI PQRPDLKFAK EATPWPREDV RRASINSFGF
GGTNAHVVLE DVEGFFSDLF GQQLPGALQL SEVTSKALVP SAMKSAVNGI PADQPPKESS
VNRLFVISAF DEAGIQRNAA SLASHLESMR AITGSDGEER LLNDLCHTLN EKRTRFDWRS
YHVADSIDSL RNSLQNPRPI RQSPAEKVVR FIFTGQGANW AGMAYDLLVY PLFRRRIQEA
AIFLKELGSD WDLYERIASQ SGELDEPTFA QSSCVAVQVA LVDLLASWNV TPQTVVGHSS
GEIAAAYCAG QISRQAAWKV AFCRGQVCAR RTDGQGRMLA AAMPVTQLEQ LVARVNKGQS
TAVKVGCYNS PKNLTLTGRA EDILRAKLEL DDVGALNRLL PVKVAYHSDY MRDAAPEYLD
LLGDLDFGDS IHADAGIKMV SSVTGRAVSA GEAQQPSYWV DNLVSPVRFS TALLASMDDP
SATGAREDAL IEIGPHSTLR TAIKETFADV REFQSIQYGS LLKRYETDGS TILRTFGMLV
CSGHKISLAA INDRRVGAKK TPRLLTGLPS YAFDHSRSMR GTSRRIEQAK FPAYKRHELL
GVPVEDTNPV EQRWRNILRP DDLPWLRMNR MNGQIHFPGV AYLLMATEAA IQRVGNTVAI
SGVRLGNVSM LAPLPIPDSA AGVEIQFSIY PMKIHANSGT DWSTFRIVSY DSAEKTWTEH
CVGSVRVETG PHESHEPHPG NATREECTES VDIAQMYSRF TTAGMDFGEY LRNIQEMKLS
PDHQACTATI TAPDIPCQAH DHYSLHPCTF ESILHALLHL CKSSQGPMVT TYIEEVLVLS
PQDTGVCGFE ACAQTQRASA TTWRSDVTIT ANTGRQQIRV TGLDLVQLPP SEDASDAESF
YVVKWKPDVK LLTSVDALRD SASMYVAQHL PTLDEHEGFQ LASGIFLLDT MDYVTRTGLP
ALPQHHQAFM QWMEKECRSI ADGTVPLLDT ALFEGIRASP DRRRELLARV AQLSARGELL
VRVGTQMVPI LEQKIDCLEV MFGPDNLMDR TYEEGLPGQI APSVAGYLHC LAHAQTGIKV
LEVGAGTGSA TKVILDSLKP TERQDGGGLV SSVSTYHFTD ISAAFFEKAR ARFPDWADIL
RPKVLNIELD PADQGFEMGS YDLVIATHVL HATADLSVSL KNIRGLLKEG GDLIVIENIQ
PDLMCSPLAF GLLPGWWRSV EPYRKTNPLI TKDQWDQELR NAGLQSRLLI DDTDEGVNEM
TAFVASRVRE PPATQHVCSI IYSSRYGGQY ELASQVARDL PPSCTASLVD LADISPEHTS
TIGIVLVGYQ GLDLSELSAH EYDRVNFLLT AFHRLLWVTC DEDEVPKSAM ASGLVRTARW
ERDHDGVNFI LLGISHRVPS ASAAVSQMIR VCDHAFFSHE LVPRNAEFRL EGSVLLTNRL
FPATGINECI ASSSRPRSKQ VALEAVQHPV KLTSIGPHQP NGFHFVEDPQ VDEPLLPDEV
KIQIRAVGLD ESDVEEMNRL IPGESAGSQG TGVVVEVGPA VHDIHVGDRV MALRTGHSGS
LQTVLRTHSS AVTQVPEGLS LADAAAVPLP FTTAYHGLVN VARLEPQDTI LIHNAGGATG
QAAVQFACML GATVYATVES DAQRQALLDY GVDRSRLLDG PSFAQQLARR GAKGSVDVLF
NLSRESLEDR DLACLSQFGR LVGVHGQGSL PAGPTNRSYA TVSIRELVQV RPKALHGTLR
TISDLLTSRA IRPITPVRAG YSELQTVLSQ IRQGNAGPWV LEPRANDTIP VAMKPLGDYQ
FDPCASYLLI GGFGGIGRSV VRWMLTRGAK NFIFLSRSGA SSVPAKQLCA DLLDAGCGVS
DTVCDVTDAT AVENALQQCG KSMPPIRGCL QCSMVLEDSM LSNMSHAQFL NAITPKVQGT
IHVASALSSV KSNLDFFVLL SSSAGIIGNR GQANYSAANA FLDAFAAHLV SRGYPATSIS
LGSVLSVGWV AENQDRLPIA LSYGAISEDL LLAILEYHMD PSWGAAQSPG TCHTVAGVRS
ARDFQRQSIP LPGFMAYPLF SPLRAIAGAS QTAEEVAEAP IAQGLRGATS MEDAVELVTR
AIVYKLARIM ALSAKEIDAQ RSLASYGVDS LVTVDLKAWF QREVGATVAS GDLLGDSTIV
QLAQQAAGGS RLVSVAMKGT E
