Polyketide-Derived Antimicrobial Metabolites from Epicoccum sorghinum: Effects of Fermentation Conditions and Non-Thermal Atmospheric Pressure Plasma (NTAPP)

Epicoccum sorghinum is a filamentous fungus known to produce structurally diverse secondary metabolites. In this study, a fungal strain isolated from Arundo donax was investigated for its antimicrobial metabolites and the effects of fermentation conditions and non-thermal atmospheric pressure plasma (NTAPP) treatment on metabolite production. Nine previously reported polyketide-related compounds isolated from E. sorghinum were evaluated for their antimicrobial activity against 16 microbial strains. Among the tested compounds, 6-(hydroxymethyl)benzene-1,2,4-triol (7) exhibited the strongest antimicrobial activity among the isolated metabolites, particularly against the Gram-positive bacterium Staphylococcus epidermidis ATCC 12228 (MIC = 50 μM). Several compounds showed moderate antifungal activity against Nakaseomyces glabrata ATCC 2001. A preliminary structure-activity relationship (SAR) analysis suggested that antimicrobial activity is closely associated with the number and positional arrangement of phenolic hydroxyl groups. Fermentation conditions significantly affected metabolite accumulation. Compound 7 showed significantly higher accumulation under solid fermentation, suggesting that solid fermentation favors the accumulation of certain phenolic-type metabolites. In addition, NTAPP treatment altered the relative abundance of previously detected metabolites in an energy-dependent manner. High-energy treatment (6000 V) increased the abundance of several metabolites, particularly epicorepoxydon A (1), whereas only a slight increase was observed for 7. Overall, this study demonstrates the antimicrobial activity of polyketide-related metabolites from E. sorghinum and highlights the influence of fermentation conditions and NTAPP treatment on fungal secondary metabolism. The combination of fermentation optimization and NTAPP stimulation represents a useful strategy for modulating the relative abundance of bioactive secondary metabolites without inducing the production of new detectable metabolites.