Protein: Non-reducing polyketide synthase pkbA (NR-PKS pkbA) (EC 2.3.1.-) (Cichorine biosynthesis cluster protein pkbA) (Q5AZ32)
Organism: Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans)
Function: Non-reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of cichorine, a phytotoxin active against knapweed, corn, and soybeans. The first step in the pathway is performed by the non-reducing polyketide synthase pkbA that condenses one acetyl-CoA starter unit with 3 malonyl-CoA units. PkbA also catalyzes one methylation step to produce 3-methylorsellinate. The nonribosomal peptide synthase-like protein cicB, the cytochrome P450 monooxygenase cicH and the O-methyltransferase cicE are involved in the conversion of 3-methylorsellinate into nidulol. CicB converts 3-methylorsellinate to a yet unidentified intermediate, cicH may play a ring-closing role for cichorine and cicE is plausibly responsible for the methylation of one of the phenol groups (Probable). The oxidoreductase cicC acts downstream with still unidentified enzymes to further convert nidulol into cichorin.
Sequence: MAPAPSALVFGSQTTLPSVEAASRLRAALLLDPRLYRMRTSIESLPEIWPALAISDPALERVAGPAEKSLRQLCRWLSHSEFPDATEISELPATFVTPFTVILHTVLYMHYTDENGSRGHADVLRAVRNNGGVQGFCTGFLTAVSVATSPDLEALSRQASVALRLAVAIGAYIDLDLLDSDVSSVAVRSRAGKKGLEETLAQFPGAYISVITDELNATVTAPRASLDALSQSLASNGLSAKRFDLRGRFHHPAHQKALEGLYNLVASNPVFQFSHSELLAPVYSNIDGQLLSSDSIIDTLLQSILVQRCDWYASISTALHKRSNGEKTSVVQFSLVECIPPSVLRQARLSVQRITDVPVQNSPATVPAPLNAVRARIQTSEPIAIIGMGCKFPGADTLDEYWQLLAQGTSMCRTMPEERFKTSSLRRSPGEKLKFWGNFVNDVDAFDHRFFKKSSREAASMDPQQRLVLQVAYQTLESAEYSGLSGIKASRDVGCYLGLCASDYTDNVASHPPNAFSSLGTLRAFLSGKISHFFGWTGPSITYDTACSSSAVAIQAACRALQTGECSMALAGGVSLYTSPNFYQNLSAASFLSPTGPTKPFDAKGDGYCRGEGVGLVFLKPLSSALADHDNIMGVIAAAAVNQNQNSTAITVPHSESQIELYRKVVSEAGLHPHDVSFVEAHGTGTPVGDPIEFTSIRTVFGGSNRANPLAIASVKGNIGHTEGAAACINNYGAAGSNAAMIVTEAPTGARSEKQGTLPKCPIYVSANTVSSLKEYCKELLRSLRGRSPDCLASLAFQLANSQNRGFPHALITSVTSKAELEDQLSAVVENRNNSLHTVAPTERPVVLAFGGQVARSVGLSRQVYDSSAVLRTHLSNCDDILTSAGLNSIFPAIFRKEPIADVVLLHSALFSAQYACAMTWIEAGVIPAALIGHSFGQLTALSVGRVLSLKDGLGLITERAKLMRDAWGPEHGSMVSVQADVQTVARLMKAAETKDPKDALEIACFNGPTSHVVVGSADAADRLEAALTQESIRYKRLAVSHGFHSKFTEPLLLGLEQCAERLTFRTPKYAIETCSSGSSWSEFNASMIVQHTRTPVYYTEALARIEAKLGACTWLEVGTGGSVAGMIRGALNVPSDHLIQAVNLAGETGTAALADATVNLWKSSHKLQFWAFHRSERECYQPLELPPYQFEKTRHWLDWKDTMTEQATVTQSTREETSVEEFLTFVKYKDSTKQQAEFRISTEHEKYSFFVKGHAVLAEPLCPAPLYIDLACKAGQMVYSDTSETLIIPSVEDLEIQAPLGVGDRVIILRLQQSPFLKTAWTFCFCSRPVMGNSAEEQLHASGTVVLRENDTKTAAEFSRFGRLVSSKRVQEMKSDPDCHILQGPVVYQLFSRVVSYADYYKGVQSVYASGAEVTGRIRLPPTVKDADTRRPLLVDNFIQTAGIHVNCLTDVGAKEVYVCTKVDRVQSAAAFTEDLANVDASWIVHSSYHPTSEKEVVNDIFVFNAATGELAMFILGAHFTRVQISSLGRVLSRANTADAAPIKVAVPVQSPALRAQPKRVLLPPLTKRSITRPTLEISEKLKKTLSRVVEVPVADIHDGGILADLGVDSLLGTEVLTEINQVFNVSIPADEFALLTDVASISKCLASYLGVHDSGSQPEDLADADSVESDSDMPTGAVTSGITTPDDAVSRLADLLAENLEYDGTIEASNNLADLGLDSILSIELANDIKKIFNCDVDMSQLNMESTFADLIALVPALNIEQSLSSVPASLTTQGSDFEMAQHAFEQIRFDYDIYTKETGFYDFWKRVYPAQSRLVLAYTVEAFAQLGCDLALMHPGDRLPKIGYLPAHEKLVQQLYNILRDGMLVATSDSGFVRSDKPVDPTSSTRLLEEINTIAPQHASEHSLLHITGSKLADCLTGTADPLNLLFRSKANRDLLAEVYLNGPMYAAISRLLCSFLGNAFSDRQSSGTFQILELGGGTGGTTGHVLDYLVRSGIPFTYTFSDVSGSFVAAARKKFAGRPYMEYQVIDIEKEPADSLTGKFHAVISTNCIHATTNLEISTGNIHRMLRPDGFVALVEFTRNMYWFDLVFGLLEGWWLFEDGRQHVIASESFWNTSMRKAGFQHVSWTDGDSFEARTLRIIAGFRAPAVNEIYTPRLDSRDTETAVESVMYKQADGIPLFADIYYPPSVSNEPRPIALMIHGGGHIMLSRKDIRPKQTAHLHTLGFLPVSIDYRLCPETTLTEGPMRDVSDAMAWARSTLCSLPLLCPGLTLDPSRVVVVGWSTGGHLAMTTAFTSIERGLSPPDAILAFYCPTDYEDRVWTQPNYPENTDVDGLSLMKYNLLEGVQDRPITAYNIPLTSRSNSKAGGTPAGGWMAPDDPRSRIVLHMNWKGQCLPVLLRGLPPSNSLSPGDAEKLISQPQPEIEEIQRVSPYAQIRRGVYRTPTFVIHGTDDDLIPYEQSVRTVQALKDMGVRAEVSVPQGKAHLFDMFKDADGSSWEVVKRGYDFLKEEVSGK
InterPro domains: - IPR016035: Acyl transferase/acyl hydrolase/lysophospholipase (homologous_superfamily) [131-1133]
- IPR014031: Beta-ketoacyl synthase, C-terminal (domain) [634-729]
- IPR014043: Acyl transferase domain (domain) [849-1158]
- IPR016039: Thiolase-like (homologous_superfamily) [377-730]
- IPR001375: Peptidase S9, prolyl oligopeptidase, catalytic domain (domain) [2421-2514]
- IPR020841: Polyketide synthase, beta-ketoacyl synthase domain (domain) [380-775]
- IPR013094: Alpha/beta hydrolase fold-3 (domain) [2200-2321]
- IPR016036: Malonyl-CoA ACP transacylase, ACP-binding (homologous_superfamily) [972-1041]
- IPR001227: Acyl transferase domain superfamily (homologous_superfamily) [2-1151]
- IPR020806: Polyketide synthase-like, phosphopantetheine-binding domain (domain) [1580-1744]
- IPR041068: Methyltransferase, fungal type, helix-turn-helix domain (domain) [1789-1874]
- IPR014030: Beta-ketoacyl synthase-like, N-terminal (domain) [381-625]
- IPR036736: ACP-like superfamily (homologous_superfamily) [1576-1788]
- IPR032088: Starter unit:ACP transacylase, SAT domain (domain) [94-250]
- IPR009081: Phosphopantetheine binding ACP domain (domain) [1574-1761]
- IPR006162: Phosphopantetheine attachment site (ptm) [1606-1731]
- IPR013217: Methyltransferase type 12 (domain) [1976-2075]
- IPR029058: Alpha/Beta hydrolase fold (homologous_superfamily) [2079-2513]
- IPR029063: S-adenosyl-L-methionine-dependent methyltransferase superfamily (homologous_superfamily) [1849-2140]
- IPR042104: Polyketide synthase, dehydratase domain superfamily (homologous_superfamily) [1218-1534]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016491 (oxidoreductase activity), GO:0016679 (oxidoreductase activity, acting on diphenols and related substances as donors), GO:0016682 (oxidoreductase activity, acting on diphenols and related substances as donors, oxygen as acceptor)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009058 (biosynthetic process), GO:0019748 (secondary metabolic process), GO:0044550 (secondary metabolite biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0032991 (protein-containing complex), GO:1902494 (catalytic complex), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:1990204 (oxidoreductase complex), GO:0005739 (mitochondrion), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle)