{"metadata":{"accession":"F5HN72","id":"CPAO_ASPOZ","source_organism":{"taxId":"5062","scientificName":"Aspergillus oryzae","fullName":"Aspergillus oryzae (Yellow koji mold)"},"name":"Beta-cyclopiazonate dehydrogenase","description":["Beta-cyclopiazonate dehydrogenase; part of the gene cluster that mediates the biosynthesis of the fungal neurotoxin cyclopiazonic acid (CPA), a nanomolar inhibitor of Ca(2+)-ATPase with a unique pentacyclic indole tetramic acid scaffold (PubMed:21608094). The hybrid two module polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) cpaS incorporates acetyl-CoA, malonyl-CoA, and tryptophan (Trp) and utilizes a C-terminal redox-incompetent reductase domain to make and release the tryptophan tetramic acid, cyclo-acetoacetyl-L-tryptophan (c-AATrp), as the first intermediate in the pathway. CpaS catalyzes a Dieckmann-type cyclization on the N-acetoacetyl-Trp intermediate bound in thioester linkage to the phosphopantetheinyl arm of the T domain to form and release c-AATrp (PubMed:19663400). CpaD then regiospecifically dimethylallylates c-AATrp to form beta-cyclopiazonic acid. CpaD discriminates against free Trp but accepts tryptophan-containing thiohydantoins, diketopiperazines, and linear peptides as substrates for C4-prenylation and also acts as regiospecific O-dimethylallyltransferase (DMAT) on a tyrosine-derived tetramic acid (PubMed:19877600, PubMed:21608094). The beta-cyclopiazonate dehydrogenase cpaO then carries out the dehydrogenation of beta-CPA to yield an unstable enimine product, which is captured by intramolecular cyclization to create the pentacyclic fused scaffold of alpha-cyclopiazonate (PubMed:21608094). Finally, the cytochrome P450 monooxygenase cpaH mediates the conversion of CPA into the less toxic 2-oxocyclopiazonic acid, the end product of the CPA pathway in A.oryza (PubMed:21608094)"],"length":455,"sequence":"MAVRIARFLGLSTVAYLALANGIDARDTISRDVIILGGGSSGTYAAIRLRDQGKTVAVVERNNYLGGHGETYYTEDNTPLNFGVEGFFNTTVTRNYLERLQVPYGRRDPAPAHEDYVNLNTGQRTEYTPGQLQDREAFAKWVDAISQFGFLDDGVYRIPEPVPEDLISPFADFVKKYHLEDAVYALFSHTSGDVLEMITLYVIQYIGVPHAAALNEGYVRPIEGIAALYKSAGKELGSDVLLETTPEAVQRFEDGVEVIVRSADGTKTLLKGKQLLVTIPPLLENLHGFPLSDQESRLFSKWQYHQYWAALVNDTGLPDDVNIVNVDTERLYGVPEEPFIWRLDNHWAPGYHNIKLVGGSEFGEDEAKAYMYERLDLLHAEGTYATHKPEIVKFASHTPVTMFVSAEEIRGGFYRQLYELQGLNSTFWTGATWASDYSTLLWGYTDEVLDQMASS","proteome":null,"gene":"cpaO","go_terms":[{"identifier":"GO:0016491","name":"oxidoreductase activity","category":{"code":"F","name":"molecular_function"}}],"protein_evidence":1,"source_database":"reviewed","is_fragment":false,"in_alphafold":true,"in_bfvd":false,"ida_accession":"5b5f43762a8111a79c1821931049e93de119ed5a","counters":{"domain_architectures":114707,"entries":7,"isoforms":0,"proteomes":0,"sets":1,"structures":0,"taxa":1,"dbEntries":{"ssf":1,"cathgene3d":3,"pfam":1,"interpro":2},"proteome":0,"taxonomy":1,"similar_proteins":114707}}}