Induced biosyntheses of a novel butyrophenone and two aromatic polyketides in the plant pathogen Stagonospora nodorum

Abstract

Fungal aromatic compounds comprise an important and structurally diverse group of secondary metabolites. Several genome sequencing projects revealed many putative biosynthetic gene clusters of fungal aromatic compounds, but many of these genes seem to be silent under typical laboratory culture conditions. To gain access to this untapped reservoir of natural products, we utilized chemical epigenetic modifiers to induce the expression of dormant biosynthetic genes. As a result, the concomitant supplementation of the histone deacetylase inhibitors suberoylanilide hydroxamic acid (500 M) and nicotinamide (50 M) to the culture medium of a fungal pathogen, Stagonospora nodorum, resulted in the isolation of three aromatic compounds (1-3), including a novel natural butyrophenone, (+)-4'-methoxy-(2S)-methylbutyrophenone (1), and two known polyketides, alternariol (2) and (-)-(3R)-mellein methyl ether (3).