Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of the cytotoxic leucine-containing cytochalasans, including aspochalasin C, aspochalasin E, TMC-169, flavichalasine F, aspergillin PZ, aspochalasin M and flavichalasine G (PubMed:32913332). The first step in the pathway is catalyzed by the hybrid PKS-NRPS ffsA that utilizes 8 units of malonyl-CoA to iteratively assemble the octaketide chain before addition of L-leucine by the C-terminal NRPS modules (PubMed:32913332). Because ffsA lacks a designated enoylreductase (ER) domain, the required activity is provided the enoyl reductase fssC (Probable). The methyltransferase (MT) domain of ffsA catalyzes the alpha-methylation at C10 and C14 using S-adenosyl-L-methionine as the methyl-donating cosubstrate (Probable). Reduction by the hydrolyase ffsE, followed by dehydration and intra-molecular Diels-Alder cyclization by the Diels-Alderase ffsF then yield the required isoindolone-fused macrocycle (By similarity). A number of oxidative steps catalyzed by the tailoring cytochrome P450 monooxygenase ffsD, the FAD-linked oxidoreductase ffsJ and the short-chain dehydrogenase/reductase ffsI, are further required to afford the final products (Probable). 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. The ffsA A domain specifically recognizes L-leucine. FfsA 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), ffsA finishes with a reductase-like domain (R) for peptide release. FssA has the following architecture: KS-MAT-DH-MT-KR-PCP-C-A-T-R. Abolishes the production of leucine-containing cytochalasans. In the C-terminal section; belongs to the NRP synthetase family.