Enhancing the Discovery of Bioactive Secondary Metabolites From Fungal Endophytes Using Chemical Elicitation and Variation of Fermentation Media.

Endophytic microorganisms are an important source of bioactive secondary metabolites. In this study, fungal endophytes obtained from A*STAR's Natural Product Library (NPL) and previously isolated from different habitats of Singapore were investigated for their diversity, antimicrobial, and cytotoxic activities. A total of 222 fungal strains were identified on the basis of sequence analysis of ITS region of the rDNA gene. The identified fungal strains belong to 59 genera distributed in 20 orders. Majority of the identified strains (99%; 219 strains) belong to the phylum , while two strains belonged to the phylum , and only one strain was from phylum. The most dominant genus was accounting for 27% of all the identified strains. Chemical elicitation using 5-azacytidine and suberoylanilide hydroxamic acid (SAHA) and variation of fermentation media resulted in the discovery of more bioactive strains. Bioassay-guided isolation and structure elucidation of active constituents from three prioritized fungal strains: sp. F6932, F5912, and F10154, led to the isolation of a known compound; palmarumycin C and five novel compounds; palmarumycin CP, muyocopronol A-C and tropicicolide. Tropicicolide displayed the strongest antifungal activity against with an IC value of 1.8 μg/ml but with a weaker activity against the presenting an IC of 7.1 μg/ml. Palmarumycin C revealed the best antiproliferative activity with IC values of 1.1 and 2.1 μg/ml against MIA PaCa-2 and PANC-1 cells, respectively.