Hybrid PKS-NRPS synthetase; 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:18854220, PubMed:21608094, PubMed:19663400). 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:18854220, PubMed:21608094, PubMed:19663400). CpaD than 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). 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). Fimally, 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). acetyl-CoA + L-tryptophan + malonyl-CoA = CO2 + 2 CoA + cyclo-acetoacetyl-L-tryptophan + H2O Secondary metabolite biosynthesis. NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D- amino acid conversion) are present within the NRP synthetase. CpaA contains also a polyketide synthase module (PKS) consisting of several catalytic domains including a ketoacyl synthase domain (KS), an acyl transferase domain (AT), a dehydratase domain (DH), a methyltransferase domain (MT), and a ketoreductase domain (KR). Instead of a thioesterase domain (TE), CpaA finishes with a reductase-like domain (RED) for peptide release. CpaA has the following architecture: KS-AT-DH-KR-PCP-C-A-T-RED. Impairs the production of cyclopiazonic acid and of its biosynthetic intermediates cyclo-acetoacetyl-L-tryptophan and beta-cyclopiazonic acid. In the C-terminal section; belongs to the NRP synthetase family.