OTAB_ASPC5
ID OTAB_ASPC5 Reviewed; 1875 AA.
AC A0A1R3RGK1;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2017, sequence version 1.
DT 03-AUG-2022, entry version 21.
DE RecName: Full=Nonribosomal peptide synthetase otaB {ECO:0000303|PubMed:30054361};
DE EC=6.3.2.- {ECO:0000269|PubMed:22983973};
DE AltName: Full=Ochratoxin A biosynthesis cluster protein B {ECO:0000303|PubMed:30054361};
GN Name=otaB {ECO:0000303|PubMed:30054361};
GN Synonyms=OTAnrps {ECO:0000303|PubMed:22983973}; ORFNames=ASPCADRAFT_132610;
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, AND DOMAIN.
RX PubMed=22983973; DOI=10.1128/aem.02508-12;
RA Gallo A., Bruno K.S., Solfrizzo M., Perrone G., Mule G., Visconti A.,
RA Baker S.E.;
RT "New insight into the ochratoxin A biosynthetic pathway through deletion of
RT a nonribosomal peptide synthetase gene in Aspergillus carbonarius.";
RL Appl. Environ. Microbiol. 78:8208-8218(2012).
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, DISRUPTION PHENOTYPE, 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: Nonribosomal peptide synthetase; 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:22983973, PubMed:30054361). OtaB is responsible for the linking
CC of phenylalanine to the dihydroisocoumarin ring (PubMed:22983973,
CC PubMed:30054361). 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:22983973,
CC ECO:0000269|PubMed:30054361, ECO:0000305|PubMed:33391201}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:22983973,
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: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module. Each module is responsible for the recognition (via the A
CC domain) and incorporation of a single amino acid into the growing
CC peptide product. Thus, an NRP synthetase is generally composed of one
CC or more modules and can terminate in a thioesterase domain (TE) that
CC releases the newly synthesized peptide from the enzyme. Occasionally,
CC epimerase (E) domains (responsible for L- to D- amino acid conversion)
CC are present within the NRP synthetase. OtaB has the following
CC architecture: A-T-C-A. {ECO:0000305|PubMed:22983973}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of ochratoxin A and
CC accumulates the intermediate ochratoxin beta.
CC {ECO:0000269|PubMed:22983973, ECO:0000269|PubMed:30054361}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; KV907504; OOF93601.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1R3RGK1; -.
DR SMR; A0A1R3RGK1; -.
DR STRING; 602072.A0A1R3RGK1; -.
DR EnsemblFungi; OOF93601; OOF93601; ASPCADRAFT_132610.
DR VEuPathDB; FungiDB:ASPCADRAFT_132610; -.
DR OMA; ERYLEYP; -.
DR OrthoDB; 4243at2759; -.
DR BioCyc; MetaCyc:MON-21061; -.
DR Proteomes; UP000188318; Unassembled WGS sequence.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:1900818; P:ochratoxin A biosynthetic process; IMP:GO_Central.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 2.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 2.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR Pfam; PF00501; AMP-binding; 2.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 2.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 2: Evidence at transcript level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW Virulence.
FT CHAIN 1..1875
FT /note="Nonribosomal peptide synthetase otaB"
FT /id="PRO_0000440606"
FT DOMAIN 724..800
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 202..590
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22983973"
FT REGION 836..1245
FT /note="Condensation"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22983973"
FT REGION 1264..1659
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22983973"
FT MOD_RES 761
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1875 AA; 204111 MW; 08BA4AFEDC8547C5 CRC64;
MTTRFPHLTD GHPVEDTTLQ SITLDVGYYP SLRSTSTEQK IHVLTIAWSI LLFAYEENDS
VRFGLEREDG WSCVAVDVHQ EVRWQDLTVK GHGVLGEDSG VNTGVCLGGQ IPMELQLVLC
MDGSDSDSDS SLSMVYQPCL LSAGQAANVA STVEAILQAL QGPNVPVGEI DMLGQRHVEC
IAGFNLAGRD LPAGCLHGIV EGQVRENGDR AAVDAWDGRL TYRELDVYAT QLSGYLVSLG
LAGSFVPLCA DKSVWAVVAM LAILKAGAAC SPLEPSHPRS RLESMVQTCG ARAVLVTEGY
ASLFQMDGVE VVVVSPDVLA LVQQTGTSLE ISPTQGSAAF LMWTSGSTGA PKGVVLEHPA
LSSSITAYAT ASQFTPRTRT FQFTSFTFTV SLCDLFGTMS RGGCVCLPSE AQRLNDLAGA
LRDFRATFCW LTSTSLASLH PSQVPDLRSI TVGGESLAEE IVARWASRCR LTVSYGTTET
CGWCLLNPGL SPTSDARILG KPTIPAAWIT HPDDPNRLVP IGAVGELLVE GPFLARGYLH
DEERTAAQFI PPPAWMARFR PGETTRLYRT NDLVRYNSDG SIRFAGRRQA HAKIRGNRIN
LTEIESHVRR ACGTADVVVD VVSTRDRVDV LTAFMLSPGP RQPLDGPLIQ QADDGFRQIV
ESALHGLEDS LPSTMIPTAF VPLSRLPLTR TNKADRRLLR EQAGQMSRAE LAQLAAHNRA
PAESPMTAAE RVMQQLWSEL MGLPLSSIGA KDSFFHLGGD SVLAIRLVPM AREHGLFLTV
LDVFHHPRLG DLVAHIKDAG SPGPDTWTAS PTAAEDVEHL KPEVARQCGV RPSDIEDVYP
CTTLQEGLMA LSAQRAGAYI LTMAYEIPPA VDVARLQEAW QTVVRALPIL RTRIVHLPSI
GFHQAVVDEP IAWHFVSSED EFRQSNRSNS MSLGSRLARF ALLQPDSAPA RLLLAVHHSI
FDRWSAPLLL AEVEKAYAGQ AVAQQHFRGF VAYVCSRPAE ESDAFWRDRL ADASPTVFPR
LPDATYLPNP TSSRDTMVVL SSSRSDFTAT SRLRLCWALL LSQHTGNTDV VFGAVSTGRS
APVAGIESLI GPTLATVPLR VQINGDASVA DALQSLQEDA TAMLPHEQRG LQNIVRIGPE
AKAACAFQSL LIVHASNSGS KLDLMGMMED EQLPELFSYG LTLSCEVQGP DRIHLQAFFD
PRMIEEGYVE VLLSQLTHAM RQVNDVPDCK LDDLNLVSPL DEERLRTWNT AWSPAQVCVH
EAIQKQSYAQ PQAEAVCSWD GSLTYASLDE RSSRLASQLH SRGVKQGAFV PLLLEKSKWT
PVAMLAVMKA GGAFVLLDAS FPVERLQSIC NQLDAPIVVS SEKHRLLAGQ LSRDLLLVSA
MDSDAPLTSL PPVHPDDAVY AVFTSGSTGT PKGVIINHAS YATGAHAHTT PASITPTARV
LQFASYAFDA SIIEHLTTLM AGGCVCIISD EERTSSLAEA VAARKATWTW LTPSVVRALE
PRDFPSLTHL CLMGESMGRT EIERWSGHVH LMQAYGPAEC SVLATLEPTL TGQSDPRNIG
TPRGCNAWIV DRDDHTRLAP VGTIGELLIE GPIVGRGYHG DVVQTQAAFC EAPEWIRQFR
PGQATPARVY KTGDLVQYSS RMDGSLLYIA RKDTQVKIRG QRLELSEVEY HARTAMASSS
DIVVDVVSPG GRQMLALFYT DDVMHDSPCM ALPMTPDQRR FLSQVRPALE ARLPSFMVPT
LWIPVTRIPL SPSRKTDRRR LQSLVGDLTP DEYKPYIIAS TSNSTQSLSK GEMKQHLSEH
EILLQRLIWQ VLEGDECSSP RPRPPISMDE LFVNIGGDSL GALSLTSLAK QSGFTFMAGD
VLGCTLGELA RMRQE
