Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of myceliothermophins, mycotoxins that contain a trans-fused decalin ring system connected to a conjugated 3-pyrrolin-2-one moiety and that have potential anti-tumor properties (PubMed:27960349). The polyketide synthase module (PKS) of the PKS-NRPS mycA is responsible for the synthesis of the octaketide backbone (PubMed:27960349). The downstream nonribosomal peptide synthetase (NRPS) module then amidates the carboxyl end of the octaketide with a leucine (PubMed:27960349). A reductase-like domain (R) at the C-terminus catalyzes the reductive release of the polyketide-amino acid intermediate (PubMed:27960349). Because mycA lacks a designated enoylreductase (ER) domain, the required activity is provided the enoyl reductase mycC (PubMed:27960349). Following mycA-catalyzed construction and release of aminoacyl polyketide aldehyde, Knoevenagel condensation yields the expected ketone (PubMed:27960349). This C18 keto acyclic precursor is the substrate of the Diels-Alderase mycB, that catalyzes the Diels-Alder cycloaddition to produce myceliothermophin E (PubMed:27960349). A yet unknown oxygenase involved in the production of myceliothermophin A, via substitution with a hydroxyl group at the C21, has still to be identified (PubMed:27960349). ATP + 12 H(+) + L-leucine + 8 malonyl-CoA + 9 NADPH + 4 S-adenosyl-L-methionine = (5S)-5-(2-methylpropyl)-3-[(2E,6R,8E,10E,12E)-6,8,10,12-tetramethyltetradeca-2,8,10,12-tetraenoyl]-2,5-dihydro-1H-pyrrol-2-one + AMP + 8 CO2 + 8 CoA + diphosphate + 7 H2O + 9 NADP(+) + 4 S-adenosyl-L-homocysteine Mycotoxin 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 (Probable). MycA 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) (Probable). Instead of a thioesterase domain (TE), mycA finishes with a reductase-like domain (R) for peptide release (Probable). MycA has the following architecture: KS-AT-DH-MT-KR-PCP-C-A-T-R (Probable). Completely abolishes the production of myceliothermophins A and E. In the C-terminal section; belongs to the NRP synthetase family.