Protein: Highly reducing polyketide synthase otaA (EC 2.3.1.-) (Ochratoxin A biosynthesis cluster protein A) (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).
Interaction partners:
- Nonribosomal peptide synthetase otaB
- Carrier domain-containing protein
- Cytochrome P450 monooxygenase otaC
- holo-[acyl-carrier-protein] synthase
Sequence:
MTFTSHPQSEPLAIIGLACKYANDINSPLDLYQQVMAARSMHGPMPPSRMDAAFYYHPSSEATGTTYAKGGYFLQSDLNAFDSPFFQLSEIDVLAMDPQQKMLLENVYHALENAGIPLKDAVSSSTSVFVGCSNNDHLALANADLLLALKGKGTGTSPSILANRISWFYDFQGTSQTIDTACSSSLVAFHQGCMDVRAGKSTMSIISGVNLMEHPAPTMYLSSLGVLSPDGRSMSFDARANGYGRGEGLGTVIIKPLTAALRDGNRIRAIVRSTGSNQDGRTPGITVPSPTAQERLIREVYKAADLDPSRTGYVEAHGTGTPVGDPLEVQAISAALGMSRDSPLYVGSVKSVVGHLEGGAGMAGLISATMAVESKTIPPVAGLQTLNPRIPQRPDLKFAKEATPWPREDVRRASINSFGFGGTNAHVVLEDVEGFFSDLFGQQLPGALQLSEVTSKALVPSAMKSAVNGIPADQPPKESSVNRLFVISAFDEAGIQRNAASLASHLESMRAITGSDGEERLLNDLCHTLNEKRTRFDWRSYHVADSIDSLRNSLQNPRPIRQSPAEKVVRFIFTGQGANWAGMAYDLLVYPLFRRRIQEAAIFLKELGSDWDLYERIASQSGELDEPTFAQSSCVAVQVALVDLLASWNVTPQTVVGHSSGEIAAAYCAGQISRQAAWKVAFCRGQVCARRTDGQGRMLAAAMPVTQLEQLVARVNKGQSTAVKVGCYNSPKNLTLTGRAEDILRAKLELDDVGALNRLLPVKVAYHSDYMRDAAPEYLDLLGDLDFGDSIHADAGIKMVSSVTGRAVSAGEAQQPSYWVDNLVSPVRFSTALLASMDDPSATGAREDALIEIGPHSTLRTAIKETFADVREFQSIQYGSLLKRYETDGSTILRTFGMLVCSGHKISLAAINDRRVGAKKTPRLLTGLPSYAFDHSRSMRGTSRRIEQAKFPAYKRHELLGVPVEDTNPVEQRWRNILRPDDLPWLRMNRMNGQIHFPGVAYLLMATEAAIQRVGNTVAISGVRLGNVSMLAPLPIPDSAAGVEIQFSIYPMKIHANSGTDWSTFRIVSYDSAEKTWTEHCVGSVRVETGPHESHEPHPGNATREECTESVDIAQMYSRFTTAGMDFGEYLRNIQEMKLSPDHQACTATITAPDIPCQAHDHYSLHPCTFESILHALLHLCKSSQGPMVTTYIEEVLVLSPQDTGVCGFEACAQTQRASATTWRSDVTITANTGRQQIRVTGLDLVQLPPSEDASDAESFYVVKWKPDVKLLTSVDALRDSASMYVAQHLPTLDEHEGFQLASGIFLLDTMDYVTRTGLPALPQHHQAFMQWMEKECRSIADGTVPLLDTALFEGIRASPDRRRELLARVAQLSARGELLVRVGTQMVPILEQKIDCLEVMFGPDNLMDRTYEEGLPGQIAPSVAGYLHCLAHAQTGIKVLEVGAGTGSATKVILDSLKPTERQDGGGLVSSVSTYHFTDISAAFFEKARARFPDWADILRPKVLNIELDPADQGFEMGSYDLVIATHVLHATADLSVSLKNIRGLLKEGGDLIVIENIQPDLMCSPLAFGLLPGWWRSVEPYRKTNPLITKDQWDQELRNAGLQSRLLIDDTDEGVNEMTAFVASRVREPPATQHVCSIIYSSRYGGQYELASQVARDLPPSCTASLVDLADISPEHTSTIGIVLVGYQGLDLSELSAHEYDRVNFLLTAFHRLLWVTCDEDEVPKSAMASGLVRTARWERDHDGVNFILLGISHRVPSASAAVSQMIRVCDHAFFSHELVPRNAEFRLEGSVLLTNRLFPATGINECIASSSRPRSKQVALEAVQHPVKLTSIGPHQPNGFHFVEDPQVDEPLLPDEVKIQIRAVGLDESDVEEMNRLIPGESAGSQGTGVVVEVGPAVHDIHVGDRVMALRTGHSGSLQTVLRTHSSAVTQVPEGLSLADAAAVPLPFTTAYHGLVNVARLEPQDTILIHNAGGATGQAAVQFACMLGATVYATVESDAQRQALLDYGVDRSRLLDGPSFAQQLARRGAKGSVDVLFNLSRESLEDRDLACLSQFGRLVGVHGQGSLPAGPTNRSYATVSIRELVQVRPKALHGTLRTISDLLTSRAIRPITPVRAGYSELQTVLSQIRQGNAGPWVLEPRANDTIPVAMKPLGDYQFDPCASYLLIGGFGGIGRSVVRWMLTRGAKNFIFLSRSGASSVPAKQLCADLLDAGCGVSDTVCDVTDATAVENALQQCGKSMPPIRGCLQCSMVLEDSMLSNMSHAQFLNAITPKVQGTIHVASALSSVKSNLDFFVLLSSSAGIIGNRGQANYSAANAFLDAFAAHLVSRGYPATSISLGSVLSVGWVAENQDRLPIALSYGAISEDLLLAILEYHMDPSWGAAQSPGTCHTVAGVRSARDFQRQSIPLPGFMAYPLFSPLRAIAGASQTAEEVAEAPIAQGLRGATSMEDAVELVTRAIVYKLARIMALSAKEIDAQRSLASYGVDSLVTVDLKAWFQREVGATVASGDLLGDSTIVQLAQQAAGGSRLVSVAMKGTE