Planta Med 2012; 78 - PI65
DOI: 10.1055/s-0032-1320752

Chemical epigenetics induce additional secondary metabolites in a filamentous fungus

KM VanderMolen 1, BA Darveaux 2, CJ Pearce 2, NH Oberlies 1
  • 1Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402
  • 2Mycosynthetix, Inc., 505 Meadowland Dr., Suite 103, Hillsborough, NC 27278

With the recent advent of complete fungi genome sequences, it has become clear that the number of gene clusters encoding for fungal secondary metabolites greatly outnumbers the known metabolites for these organisms. Small molecule epigenetic modifiers can be used to inhibit various proteins that subdue DNA transcription, upregulating the production of diverse secondary metabolites. This study tested the effect of three epigenetic modifiers, including the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA), the DNA methyltransferase inhibitor 5-azacytidine, and the proteasome inhibitor bortezomib, on the secondary metabolome of a filamentous fungus shown to produce polyketide-derived resorcylic acid lactones. A suite of growth conditions was explored, including a rice medium, the defined medium Czapek Dox, and potato dextrose broth (PDB); PDB demonstrated optimal metabolite production. The fungus (MSX 63935, Pleosporales), collected from leaf litter, was grown in PDB in the presence of several concentrations of each modifier. The organic extracts of these growths were analyzed by ultrahigh performance liquid chromatography (UPLC) and compared to a negative control growth. Each of the modifying agents induced the fungus to produce additional secondary metabolites.