PKS-NRPS hybrid synthetase; part of the gene cluster that mediates the biosynthesis of pyrophen and campyrone B, which represent a class of fungal amino acid-derived alpha-pyrone natural products (PubMed:32159958). The first step of pyrophen biosynthesis is catalyzed by the PKS-NRPS hybrid synthetase ATPKS that uptakes and condensates L-phenylalanine and malonyl-CoA in order to produce desmethyldesacetylpyrophen (PubMed:32159958). Although the A domain does not discriminate between 2 enantiomeric phenylalanines, the downstream KS domain must play a gate keeping role to stereoselectively accept the L-phenylalanyl-S-phosphopantetheine (Ppant)-T domain intermediate for chain elongation (PubMed:32159958). The resulting amino acid derived diketide is off-loaded through lactonization to yield the alpha-pyrone intermediate desmethyldesacetylpyrophen (PubMed:32159958). The cluster-specific O-methyltransferase (OMT) then methylates desmethyldesacetylpyrophen to desacetylpyrophen, which is further acetylated to pyrophen by an endogenous yet unidentified N-acetyltransferase (PubMed:32159958). ATPKS has relaxed substrate specificity to activate and extend branched-chain amino acid L-leucine to produce small amounts of campyrone B (PubMed:32159958). Secondary metabolite biosynthesis. The architecture of ATPKS is the following one: adenylation (A), phosphopantetheine-binding/thiolation (T), beta-ketoacyl synthase (KS), malonyl-CoA:ACP transacylase (MAT), ketoreductase (KR) domain, and thioester reductase (TE) domains. In the C-terminal section; belongs to the NRP synthetase family.