Epigenetic modifier-induced biosynthesis of novel fusaric acid derivatives in endophytic fungi from Datura stramonium L.

ABSTRACT: The treatment of fungi with DNA methyltransferase (DNMT) and/or histone deacetylase (HDAC) inhibitors is a promising way to activate secondary metabolite biosynthetic pathways that are dormant under normal conditions. In this study, we included an HDAC inhibitor, suberoylanilide hydroxamic acid (SBHA), in the culture medium of endophytic fungi isolated from the medicinal plant Datura stramonium L. The production of two compounds was induced in the culture supplemented with SBHA, and their structures were determined to be the fusaric acid derivatives 5-butyl-6-oxo-1,6-dihydropyridine-2-carboxylic acid and 5-(but-9-enyl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid. The result confirmed that the use of chemical epigenetic modifiers is an effective technique for promoting the expression of silent biosynthetic pathways to produce unique secondary metabolites. GRAPHICAL ABSTRACT: [Image: see text]