Molecular and Chemical Characterization of the Biosynthesis of the 6-MSA-Derived Meroterpenoid Yanuthone D in Aspergillus niger

Secondary metabolites in filamentous fungi constitute a rich source of bioactive molecules. We have deduced the genetic and biosynthetic pathway of the antibiotic yanuthone D from Aspergillus niger. Our analyses show that yanuthone D is a meroterpenoid derived from the polyketide 6-methylsalicylic acid (6-MSA). Yanuthone D formation depends on a cluster composed of ten genes including yanA and yanl, which encode a 6-MSA polyketide synthase and a previously undescribed O-mevalon transferase, respectively. In addition, several branching points in the pathway were discovered, revealing five yanuthones (F, G, H, I, and J). Furthermore, we have identified another compound (yanuthone X-1) that defines a class of yanuthones that depend on several enzymatic activities encoded by genes in the yan cluster but that are not derived from 6-MSA.