Chemical and Physical Modulation of Antibiotic Activity in Emericella Species

The addition of epigenetic modifying agents and ion-exchange resins to culture media and solid-state fermentations have been promoted as ways to stimulate expression of latent biosynthetic gene clusters and to modulate secondary metabolite biosynthesis. We asked how combination of these treatments would affect a population of screening isolates and their patterns of antibiosis relative to fermentation controls. A set of 43 Emericella strains, representing 25 species and varieties, were grown on a nutrient-rich medium comprising glucose, casein hydrolysate, urea, and mineral salts. Each strain was grown in untreated agitated liquid medium, a medium treated with suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, 5-azacytidine, a DNA methylation inhibitor, an Amberlite non-ionic polyacrylate resin, and the same medium incorporated into an inert static vermiculite matrix. Species-inherent metabolic differences more strongly influenced patterns of antibiosis than medium treatments. The antibacterial siderophore, desferritriacetylfusigen (1), was detected in most species in liquid media, but not in the vermiculite medium. The predominant antifungal component detected was echinocandin B. Some species produced this antifungal regardless of treatment, although higher quantities were often produced in vermiculite. Several species are reported for the first time to produce echinocandin B (3). A new echinocandin analog, echinocandin E (2), was identified from E. quadrilineata.