Molecular and chemical characterization of the biosynthesis of the 6-MSA-derived meroterpenoid yanuthone D in Aspergillus niger


Holm DK1, Petersen LM2, Klitgaard A3, Knudsen PB4, Jarczynska ZD1, Nielsen KF3, Gotfredsen CH5, Larsen TO6, Mortensen UH7.
Chem Biol. 2014 Apr 24;21(4):519-29. Epub 2014 Mar 27.


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 yanI, 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 X1) 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.