Genome mining and molecular characterization of the biosynthetic gene cluster of a diterpenic meroterpenoid, 15-deoxyoxalicine B, in .

Meroterpenoids are a class of secondary metabolites that are produced from polyketide and terpenoid precursors. 15-Deoxyoxalicine B () belongs to one structural group consisting of a unique pyridinyl-α-pyrone polyketide subunit and a diterpenoid subunit connected through a characteristic asymmetric spiro carbon atom. An understanding of the genes involved in the biosynthesis of this class of compounds should provide a means to facilitate engineering of second-generation molecules and increasing production of first-generation compounds. We found that the filamentous fungus produces 15-deoxyoxalicine B (). Using targeted gene deletions, we have identified a cluster of 12 responsible contiguous genes. This gene cluster includes one polyketide synthase gene which we have designated . Chemical analysis of wild-type and gene deletion mutant extracts enabled us to isolate and characterize 7 additional metabolites that are either intermediates or shunt products of the biosynthetic pathway. Two of the compounds identified have not been reported previously. Our data have allowed us to propose a biosynthetic pathway for 15-deoxyoxalicine B ().