Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of the tetramic acid Sch210972, a potential anti-HIV fungal natural product that contains a decalin core (PubMed:26360642). The PKS module of cghG together with the enoylreductase cghC catalyze the formation of the polyketide unit which is then conjugated to 4-hydroxyl-4-methyl glutamate (HMG) by the condensation domain of the cghG NRPS module (PubMed:26360642). One unique structural feature of Sch210972 is the tetramic acid motif proposed to be derived from the non-proteinogenic amino acid HMG, by a Dieckmann-type condensation catalyzed by the reductase domain of cghG (PubMed:26360642). The aldolase cghB catalyzes the aldol condensation of 2 molecules of pyruvic acid to yield the intermediate 4-hydroxyl-4-methyl-2-oxoglutarate (HMOG), which can then be stereoselectively transaminated by an unidentified enzyme to form HMG (PubMed:26360642). The Diels-Alderase cghA then uses the Dieckmann product released by cghG as substrate and catalyzes the Diels-Alder cycloaddition to form the decalin ring of Sch210972 (PubMed:26360642). CghA also suppresses the nonenzymatic formation of the alternative stereoisomer (PubMed:26360642). (2S,4S)-4-hydroxy-4-methylglutamate + ATP + 11 H(+) + 8 malonyl-CoA + 8 NADPH + 3 S-adenosyl-L-methionine = (2S)-3-[(2S)-3,5-dioxo-4-[(2E,4R,6R,8E,10E,12E)-4,6,12-trimethyltetradeca-2,8,10,12-tetraenoyl]pyrrolidin-2-yl]-2-hydroxy-2-methylpropanoate + AMP + 8 CO2 + 8 CoA + diphosphate + 6 H2O + 8 NADP(+) + 3 S-adenosyl-L-homocysteine 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), cghG finishes with a reductase-like domain (R) for peptide release. CghG 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.