Nicotinamide and Sodium Butyrate Double the Pool of Treatment-Exclusive Metabolites in the Endophytic Fungus Curvularia sp. G6-32.

Endophytic fungi are prolific sources of bioactive natural products, but many biosynthetic gene clusters remain silent under laboratory conditions. Following the OSMAC approach, the epigenetic modifiers nicotinamide and sodium butyrate (10 µM) were added to triplicate liquid cultures of Curvularia sp. G6-32, an endophyte of Sapindus saponaria, and the crude extracts were analyzed by UHPLC-MS/MS with Mzmine 3 processing and GNPS molecular networking. In total, 712 features were detected: 474 common to all treatments, 65 exclusive to the control, and 154 occurring only in the presence of the modifiers (7 nicotinamide, 9 sodium butyrate, 138 both). PCA, ANOVA (p < 0.05) and volcano analysis (Student's t-test, p < 0.05, n = 3) separated the treated cultures from the control. Among 34 putatively identified compounds, diketopiperazines were the most abundant family (15 ionic species), whereas loliolide, γ-linolenic acid and N-(3-hydroxytetradecanoyl)-DL-homoserine lactone illustrate the diversification elicited by both modifiers.