OTAB_ASPNC
ID OTAB_ASPNC Reviewed; 1880 AA.
AC A2R6H0;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 25-MAY-2022, entry version 92.
DE RecName: Full=Nonribosomal peptide synthetase otaB {ECO:0000303|PubMed:27667988};
DE EC=6.3.2.- {ECO:0000305|PubMed:27667988};
DE AltName: Full=Ochratoxin biosynthesis cluster protein 2 {ECO:0000303|PubMed:27667988};
DE AltName: Full=Ochratoxin biosynthesis cluster protein B {ECO:0000303|PubMed:33391201};
GN Name=otaB {ECO:0000303|PubMed:33391201};
GN Synonyms=ota2 {ECO:0000303|PubMed:27667988}; ORFNames=An15g07910;
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.
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 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 [5]
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: 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:27667988). OtaB is responsible for the linking of phenylalanine
CC to the dihydroisocoumarin ring (By similarity). The pathway begins with
CC the highly reducing polyketide synthase otaA that catalyzes the
CC formation of the isocoumarin group during the initial stages of
CC biosynthesis, starting from one acetate and 4 malonate units, to
CC originate the characteristic pentaketide skeleton 7-methylmellein (7-
CC MM) of the OTA molecule. The newly identified cyclase otaY might be
CC involved in the polyketide cyclization reaction during the initial
CC steps of the OTA biosynthesis. 7-MM is then oxidized into 7-
CC carboxymellein (also called ochratoxin beta) by the cytochrome P450
CC monooxygenase otaC. The NRPS encoded by the otaB gene is involved in
CC the linking of phenylalanine to the dihydroisocoumarin ring. The
CC reaction catalyzed by NRPS results in the production of ochratoxin B
CC (OTB), which is the non-chlorinated analog of OTA and which
CC subsequently serves as the substrate of the halogenase otaD for
CC chlorination activity to form the final molecular structure of OTA,
CC containing a chlorine atom in the C-5 position of the molecule
CC (PubMed:27667988, PubMed:33391201) (Probable).
CC {ECO:0000250|UniProtKB:A0A1R3RGK1, ECO:0000269|PubMed:27667988,
CC ECO:0000305|PubMed:27667988, ECO:0000305|PubMed:33391201}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000250|UniProtKB:A0A1R3RGK1}.
CC -!- INDUCTION: 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. {ECO:0000269|PubMed:35143724}.
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:0000250|UniProtKB:A0A1R3RGK1}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; AM270352; CAK42678.1; -; Genomic_DNA.
DR AlphaFoldDB; A2R6H0; -.
DR SMR; A2R6H0; -.
DR PaxDb; A2R6H0; -.
DR EnsemblFungi; CAK42678; CAK42678; An15g07910.
DR VEuPathDB; FungiDB:An15g07910; -.
DR HOGENOM; CLU_000022_0_12_1; -.
DR Proteomes; UP000006706; Chromosome 3R.
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; ISS:GO_Central.
DR GO; GO:0019748; P:secondary metabolic process; NAS:AspGD.
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 InterPro; IPR006162; Ppantetheine_attach_site.
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.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 2: Evidence at transcript level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW Virulence.
FT CHAIN 1..1880
FT /note="Nonribosomal peptide synthetase otaB"
FT /id="PRO_0000440607"
FT DOMAIN 728..804
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 205..594
FT /note="Adenylation 1"
FT /evidence="ECO:0000255"
FT REGION 840..1250
FT /note="Condensation"
FT /evidence="ECO:0000255"
FT REGION 1269..1665
FT /note="Adenylation 2"
FT /evidence="ECO:0000255"
FT MOD_RES 765
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1880 AA; 205814 MW; 6FE2519B7BB232E2 CRC64;
MDLRTGYMFP CLTDGQFVED DTLHSVALGI DSPISLSNGP DGEWARELSI AWAILLFTYN
EQEAVEFACL RNQHWFCVDA KMNRDLSWKD IEIHEGGTSD GRQVNTGLCL SQEGATPIPT
RLQLVLVGSI SGGGLSLEYR PNLLSAEQAA NVASTLETIM RALQGRTVSI GSIDVLSERN
ITDLNRFAVA RRALPEGCLD DIITAQAVER GNSIAIDSWD GTLSYQELDT LSTLLAKYLR
SLDLSGTYVP LCADKSAWAV VAMLAILKAG AACSPLDPSH PRSRLQSMVQ LCDAKAVIAT
ERHASLLQMD GVEVVVVGPD MSSFLQHQIS PAEAPGPSHR DVAFLMWTSG STGAPKGVIL
EHTALFMSIS AYAAANQFSA ETRCFQFTSF TFAVSLCDIF GTLSQGGCLC MPSETQRLTD
LTGALRELHA TFCWLTSTSL ADLNPHDLPD LRSVTVGGES LSRELVARWA THLRLTVSYG
TTETAGWCLL NTGLSPTGDA RTLGRPTIPG VWIAHPDNVN RLVPVGAVGE LLVEGPFLAQ
GYLDDEERTA AHFIPPPSWM TQFRPQEVTR LYRTNDLVRY NSDGSVSFVG RRQAHAKIRG
NRISLPEIEA QVRHSCKDAQ AVVELVTTKD QVEMLTAFLV VSGQESLSEA PLICPPNDCF
RETVTNSLSV LEQSLPSYMV PTVFVPLSHI PLTRTNKADR HVLRKLAEAM SRADLVQLMT
KPRPVEQLPL SPLERQIQGL WADLTNIPAE SIGPDDNFFH LGGDSVLAIH LVPLARRHGL
SLTVQDVFRY PKMKELGAHL EQEASQGSQR SKSQPIASFD PTPWKSVAAQ QCGIDELAIE
DVYPCTALQE GLMALSAQRT GAYILSMAQN LSPTVDLGRL LEAWQTVVKA VPILRTRIVR
LTNEGFHQAV VDESIEWQSV KSEAEFRRMN QLNPLGLGTR LVRFALLLSA ADQPSRLLLA
MHHSVFDRWS GPLLVRAVED AYQGQPVMPQ YFKDFVSYVS TCPREEVDAF WRHQLSDADP
TVFPPTPEPN YLPSPTKSSE RIILLPLSRT HVTITTKLRL CWALVLSQHT GNADVVFGAV
STGRSARVEG IESLIGPTLA TVPFRVRIDG SAMVSDALQA LQDDAATMLP YEQRGLQNIA
RISRETRAAC NFQNLLIVHA PDSRGHSTIL KITDDQQLLD LFSYGLTLSC EVLDQDRIQC
QAFFDPNMLE HAYVKVLLDQ LAHAVRQIHA VPDCKVGEIS LLSPQDQQQL QEWNPPIPRT
GLTIHETIQR QCLAHPQKEA VCSWDGSITY RALNELSSSL ASQILQRCGQ PTSFVPLLME
RSKWTAVTML AVMKAGKAFV LLDASFPVER LQSICCQLDA TLILSSSKHA DVAQRLVSNP
LIVDAIIGLP GPSLALPVVH PDATLYAVFT SGSTGRPKAV LISHASYGSG AEAHIPAALI
TPATRVLQFA SYAFDASIIE HLSTFMAGGC VCVLSDPERT SSLAEAVAAQ RANFAWLTPS
VTRFIDPQDF PTMDRLCLMG ESMRRSEIER WSSRVNLMQA YGPAECSVLA TLRPSLTTQS
DPRNIGCARG CHAWVVDPEN HTRLLPIGAV GELIIEGPIV GQGYHGSPEQ TQAAFPPVPD
WLSDYHDGDL SQVRVYKTGD LVQYSPKLDG SLLFIGRKDR QVKLRGQRLE LSEVEYHAYH
TLAGTWELVV ELINSQHNPA LALFLAEKQD SPKPCGVLSM TPAWRSVMSR LRDTLASRLP
PYMVPTVWIP ITQIPLSSSQ KTDRRSLQSL AGDLSAEQYQ TYILASSSEA TPGLTHSHLK
EVPLNENELV LQDLVRQVFT GEDGSLSVAS IPMDGLFTDI GGDSLGALAL TSLAKQHGFH
FTAGDVLGSS LGELASLRHT
