Non-reducing polyketide synthase; part of the cla gene cluster that produces clavatol and ortho-quinone methide (PubMed:30811183). The clavatol biosynthesis cluster cla and the terrestric acid cluster tra are both involved in the production of peniphenones and penilactones (PubMed:30811183). The non-reducing PKS claF is responsible for the formation of clavatol from successive condensations of 3 malonyl-CoA units, presumably with a simple acetyl-CoA starter unit, and 2 methylation steps (PubMed:30811183). The esterase claE probably collaborates with claF by catalyzing the hydrolysis of ACP-bound acyl intermediates to free the ACP from stalled intermediates (By similarity). The clavatol oxidase claD then converts clavatol to hydroxyclavatol (PubMed:30811183). Spontaneous dehydration of hydroxyclavatol leads to the accumulation of the highly active ortho-quinone methide (PubMed:30811183, PubMed:31860310). On the other hand, the PKS-NRPS hybrid traA is involved in the formation of crustosic acid, with the help of traB and traD (PubMed:30811183). The polyketide synthase module (PKS) of traA is responsible for the synthesis of the polyketide backbone via the condensation of an acetyl-CoA starter unit with 3 malonyl-CoA units (PubMed:30811183). The downstream nonribosomal peptide synthetase (NRPS) module then amidates the carboxyl end of the polyketide with L-malic acid (PubMed:30811183). Because traA lacks a designated enoylreductase (ER) domain, the required activity is provided the enoyl reductase traG (By similarity). Crustosic acid undergoes decarboxylation and isomerization to the terrestric acid, catalyzed by the 2-oxoglutarate-dependent dioxygenase traH (PubMed:30811183). Both acids are further converted to the 2 gamma-butyrolactones (R)-5-methyltetronic acid and (S)-5-carboxylmethyltetronic acid, with involvement of the cytochrome P450 monooxygenase claJ (PubMed:30811183). Spontaneous addition of the methide to these gamma-butyrolactones leads to peniphenone D and penilactone D, which undergo again stereospecific attacking by methide to give penilactones A and B (PubMed:30811183, PubMed:31860310). acetyl-CoA + AH2 + H(+) + 3 malonyl-CoA + 2 S-adenosyl-L-methionine = A + clavatol + 3 CO2 + 4 CoA + H2O + 2 S-adenosyl-L-homocysteine Binds 1 phosphopantetheine covalently. Secondary metabolite biosynthesis. Multidomain protein; including an N-terminal starter unit:ACP transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a malonyl-CoA:ACP transacylase (MAT) domain, a product template domain, a acyl carrier protein (ACP) domain, a methyltransferase domain (CMeT) and a reductive NADPH-binding domain that is required for NADPH-dependent product release. Completely abolishes the production of clavatol, as well as of the clavatol-derived compounds peniphenone D, penilactone D, penilactone A and penilactone B (PubMed:30811183). Leads to the accumulation of the 2 tetronic acids terrestric acid and crustosic acid (PubMed:30811183).