Epigenetic stimulation of polyketide production in Chaetomium cancroideum by an NAD+-dependent HDAC inhibitor

Abstract

Exposure of the fungus Chaetomium cancroideum to an NAD⁺-dependent HDAC inhibitor, nicotinamide, enhanced the production of aromatic and branched aliphatic polyketides, which allowed us to isolate new secondary metabolites, chaetophenol G and cancrolides A and B. Their structures were determined using spectroscopic analyses, and their absolute configuration was elucidated by electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and chemical transformations. Biosynthesis of the branched aliphatic polyketide skeletons in cancrolides A and B was evidenced by conducting a feeding experiment using compounds labeled with a ¹³C stable isotope.