Hybrid PKS-NRPS synthetase; part of the gene cluster that produces the tetronate natural products trihazones (PubMed:33570538). The PKS-NRPS synthetase thnA with the help of the trans-enoyl reductase thnE are responsible for the synthesis of the carboxylmethyl containing trihazone A (PubMed:33570538). The PKS portion of thnA synthesizes beta-keto-triene chain from one acetyl-CoA and 6 equivalents of malonyl-CoA, in collaboration with thnE, which selectively reduces the enoyl intermediate during the first and fourth iteration of the PKS (PubMed:33570538). The NRPS domain selects and activates malate, of which the alpha-hydroxyl group attacks the completed polyketide acyl-S-ACP chain to form the ester product (PubMed:33570538). Intramolecular Dieckmann cyclization catalyzed by the terminal reductase domain releases the product as trihazone A from the PKS-NPRS (PubMed:33570538). The pathway begins with the formation of trihazone A by the hybrid PKS-NRPS synthetase thnA and the trans-enoyl reductase thnE. Trihazone A is further decarboxylated by the 2-oxoglutarate-dependent dioxygenase thnC to produce trihazone D. The function of the FAD-dependent monooxygenase thnD has still to be identified (PubMed:33570538). 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. ThnA 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), traA finishes with a reductase-like domain (R) for peptide release. ThnA has the following architecture: KS-AT-DH-KR-PCP-C-A-T-R. In the C-terminal section; belongs to the NRP synthetase family.