Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of varicidin A, an antifungal natural product containing a cis-octahydrodecalin core (PubMed:30609896). The PKS module of pvhA together with the enoylreductase pvhC catalyze the formation of the polyketide unit which is then conjugated to L-isoleucine by the condensation domain of the NRPS module (PubMed:30609896). Activity of the Dieckmann cyclase domain (RED) of pvhA results in release of an acyclic tetramate (PubMed:30609896). The cytochrome P450 monooxygenase pvhE then catalyzes the oxidation of the C21 methyl group to a to carboxylate group (PubMed:30609896). The methyltransferase pvhD then further methylates the pvhE product (PubMed:30609896). The Diels-Alderase pvhB is able to catalyzes Diels-Alder cycloaddition using both pvhE and pvhD products as substrates to form the decalin ring, yielding varicidin B and A, respectively (PubMed:30609896). 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. CcsA 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), pvhA finishes with a reductase-like domain (R) for peptide release. PvhA has the following architecture: KS-MAT-DH-MT-KR-PCP-C-A-T-R. In the C-terminal section; belongs to the NRP synthetase family.