Protein: Highly reducing polyketide synthase otaA (A0A1R3RGK0)
Organism: Aspergillus carbonarius (strain ITEM 5010)
Function: Highly reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of ochratoxin A (OTA), a mycotoxin composed of a chlorinated type I polyketide dihydroisocoumarin moiety linked to L-phenylalanine, and demonstrated to have nephrotoxic, immunotoxic, genotoxic, neurotoxic, and teratogenic properties. OtaA catalyzes the condensation of one acetate and 4 malonate units to form the isocoumarin group. The pathway begins with the highly reducing polyketide synthase otaA that catalyzes the formation of the isocoumarin group during the initial stages of biosynthesis, starting from one acetate and 4 malonate units, to originate the characteristic pentaketide skeleton 7-methylmellein (7-MM) of the OTA molecule. The newly identified cyclase otaY might be involved in the polyketide cyclization reaction during the initial steps of the OTA biosynthesis. 7-MM is then oxidized into 7-carboxymellein (also called ochratoxin beta) by the cytochrome P450 monooxygenase otaC. The NRPS encoded by the otaB gene is involved in the linking of phenylalanine to the dihydroisocoumarin ring. The reaction catalyzed by NRPS results in the production of ochratoxin B (OTB), which is the non-chlorinated analog of OTA and which subsequently serves as the substrate of the halogenase otaD for chlorination activity to form the final molecular structure of OTA, containing a chlorine atom in the C-5 position of the molecule (Probable)
Sequence: MTFTSHPQSEPLAIIGLACKYANDINSPLDLYQQVMAARSMHGPMPPSRMDAAFYYHPSSEATGTTYAKGGYFLQSDLNAFDSPFFQLSEIDVLAMDPQQKMLLENVYHALENAGIPLKDAVSSSTSVFVGCSNNDHLALANADLLLALKGKGTGTSPSILANRISWFYDFQGTSQTIDTACSSSLVAFHQGCMDVRAGKSTMSIISGVNLMEHPAPTMYLSSLGVLSPDGRSMSFDARANGYGRGEGLGTVIIKPLTAALRDGNRIRAIVRSTGSNQDGRTPGITVPSPTAQERLIREVYKAADLDPSRTGYVEAHGTGTPVGDPLEVQAISAALGMSRDSPLYVGSVKSVVGHLEGGAGMAGLISATMAVESKTIPPVAGLQTLNPRIPQRPDLKFAKEATPWPREDVRRASINSFGFGGTNAHVVLEDVEGFFSDLFGQQLPGALQLSEVTSKALVPSAMKSAVNGIPADQPPKESSVNRLFVISAFDEAGIQRNAASLASHLESMRAITGSDGEERLLNDLCHTLNEKRTRFDWRSYHVADSIDSLRNSLQNPRPIRQSPAEKVVRFIFTGQGANWAGMAYDLLVYPLFRRRIQEAAIFLKELGSDWDLYERIASQSGELDEPTFAQSSCVAVQVALVDLLASWNVTPQTVVGHSSGEIAAAYCAGQISRQAAWKVAFCRGQVCARRTDGQGRMLAAAMPVTQLEQLVARVNKGQSTAVKVGCYNSPKNLTLTGRAEDILRAKLELDDVGALNRLLPVKVAYHSDYMRDAAPEYLDLLGDLDFGDSIHADAGIKMVSSVTGRAVSAGEAQQPSYWVDNLVSPVRFSTALLASMDDPSATGAREDALIEIGPHSTLRTAIKETFADVREFQSIQYGSLLKRYETDGSTILRTFGMLVCSGHKISLAAINDRRVGAKKTPRLLTGLPSYAFDHSRSMRGTSRRIEQAKFPAYKRHELLGVPVEDTNPVEQRWRNILRPDDLPWLRMNRMNGQIHFPGVAYLLMATEAAIQRVGNTVAISGVRLGNVSMLAPLPIPDSAAGVEIQFSIYPMKIHANSGTDWSTFRIVSYDSAEKTWTEHCVGSVRVETGPHESHEPHPGNATREECTESVDIAQMYSRFTTAGMDFGEYLRNIQEMKLSPDHQACTATITAPDIPCQAHDHYSLHPCTFESILHALLHLCKSSQGPMVTTYIEEVLVLSPQDTGVCGFEACAQTQRASATTWRSDVTITANTGRQQIRVTGLDLVQLPPSEDASDAESFYVVKWKPDVKLLTSVDALRDSASMYVAQHLPTLDEHEGFQLASGIFLLDTMDYVTRTGLPALPQHHQAFMQWMEKECRSIADGTVPLLDTALFEGIRASPDRRRELLARVAQLSARGELLVRVGTQMVPILEQKIDCLEVMFGPDNLMDRTYEEGLPGQIAPSVAGYLHCLAHAQTGIKVLEVGAGTGSATKVILDSLKPTERQDGGGLVSSVSTYHFTDISAAFFEKARARFPDWADILRPKVLNIELDPADQGFEMGSYDLVIATHVLHATADLSVSLKNIRGLLKEGGDLIVIENIQPDLMCSPLAFGLLPGWWRSVEPYRKTNPLITKDQWDQELRNAGLQSRLLIDDTDEGVNEMTAFVASRVREPPATQHVCSIIYSSRYGGQYELASQVARDLPPSCTASLVDLADISPEHTSTIGIVLVGYQGLDLSELSAHEYDRVNFLLTAFHRLLWVTCDEDEVPKSAMASGLVRTARWERDHDGVNFILLGISHRVPSASAAVSQMIRVCDHAFFSHELVPRNAEFRLEGSVLLTNRLFPATGINECIASSSRPRSKQVALEAVQHPVKLTSIGPHQPNGFHFVEDPQVDEPLLPDEVKIQIRAVGLDESDVEEMNRLIPGESAGSQGTGVVVEVGPAVHDIHVGDRVMALRTGHSGSLQTVLRTHSSAVTQVPEGLSLADAAAVPLPFTTAYHGLVNVARLEPQDTILIHNAGGATGQAAVQFACMLGATVYATVESDAQRQALLDYGVDRSRLLDGPSFAQQLARRGAKGSVDVLFNLSRESLEDRDLACLSQFGRLVGVHGQGSLPAGPTNRSYATVSIRELVQVRPKALHGTLRTISDLLTSRAIRPITPVRAGYSELQTVLSQIRQGNAGPWVLEPRANDTIPVAMKPLGDYQFDPCASYLLIGGFGGIGRSVVRWMLTRGAKNFIFLSRSGASSVPAKQLCADLLDAGCGVSDTVCDVTDATAVENALQQCGKSMPPIRGCLQCSMVLEDSMLSNMSHAQFLNAITPKVQGTIHVASALSSVKSNLDFFVLLSSSAGIIGNRGQANYSAANAFLDAFAAHLVSRGYPATSISLGSVLSVGWVAENQDRLPIALSYGAISEDLLLAILEYHMDPSWGAAQSPGTCHTVAGVRSARDFQRQSIPLPGFMAYPLFSPLRAIAGASQTAEEVAEAPIAQGLRGATSMEDAVELVTRAIVYKLARIMALSAKEIDAQRSLASYGVDSLVTVDLKAWFQREVGATVASGDLLGDSTIVQLAQQAAGGSRLVSVAMKGTE
InterPro domains: - IPR013217: Methyltransferase type 12 (domain) [1441-1553]
- IPR020843: Enoylreductase domain (domain) [1838-2141]
- IPR014043: Acyl transferase domain (domain) [571-892]
- IPR016035: Acyl transferase/acyl hydrolase/lysophospholipase (homologous_superfamily) [570-870]
- IPR036291: NAD(P)-binding domain superfamily (homologous_superfamily) [1938-2380]
- IPR001227: Acyl transferase domain superfamily (homologous_superfamily) [570-889]
- IPR020841: Polyketide synthase, beta-ketoacyl synthase domain (domain) [9-434]
- IPR016039: Thiolase-like (homologous_superfamily) [2-437]
- IPR011032: GroES-like superfamily (homologous_superfamily) [1837-1971]
- IPR020807: Polyketide/metazoan fatty acid synthase-like, dehydratase domain (domain) [957-1134]
- IPR013154: Alcohol dehydrogenase-like, N-terminal (domain) [1857-1917]
- IPR018201: Beta-ketoacyl synthase, active site (active_site) [173-189]
- IPR032821: Polyketide synthase, C-terminal extension (domain) [387-543]
- IPR014031: Beta-ketoacyl synthase, C-terminal (domain) [269-383]
- IPR016036: Malonyl-CoA ACP transacylase, ACP-binding (homologous_superfamily) [694-762]
- IPR009081: Phosphopantetheine binding ACP domain (domain) [2453-2530]
- IPR020806: Polyketide synthase-like, phosphopantetheine-binding domain (domain) [2459-2530]
- IPR014030: Beta-ketoacyl synthase-like, N-terminal (domain) [10-259]
- IPR029063: S-adenosyl-L-methionine-dependent methyltransferase superfamily (homologous_superfamily) [1322-1610]
- IPR013968: Polyketide synthase-like, ketoreductase domain (domain) [2165-2344]
Interaction partners: - Nonribosomal peptide synthetase otaB
- Carrier domain-containing protein
- Cytochrome P450 monooxygenase otaC
- holo-[acyl-carrier-protein] synthase
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0016491 (oxidoreductase activity), GO:0016746 (acyltransferase activity), GO:0016741 (transferase activity, transferring one-carbon groups), GO:0016747 (acyltransferase activity, transferring groups other than amino-acyl groups), GO:0008168 (methyltransferase activity), GO:0008757 (S-adenosylmethionine-dependent methyltransferase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:0006575 (cellular modified amino acid metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:1901564 (organonitrogen compound metabolic process), GO:0044283 (small molecule biosynthetic process), GO:0046483 (heterocycle metabolic process), GO:0006082 (organic acid metabolic process), GO:0044249 (cellular biosynthetic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0043603 (amide metabolic process), GO:1901566 (organonitrogen compound biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0042398 (cellular modified amino acid biosynthetic process), GO:0016053 (organic acid biosynthetic process), GO:0043436 (oxoacid metabolic process), GO:0018130 (heterocycle biosynthetic process), GO:0043604 (amide biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0019752 (carboxylic acid metabolic process), GO:0046394 (carboxylic acid biosynthetic process), GO:0072330 (monocarboxylic acid biosynthetic process), GO:0032787 (monocarboxylic acid metabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005622 (intracellular anatomical structure)