Metabolomics and Dereplication Study of the Endophytic Fungus Aspergillus chevelieri in Search of Bioactive Natural Compounds

Objectives: This study aimed to point the significant rule of metabolomics tools to assess the chemistry of the bioactive metabolites produced by endophytic fungus Aspergillus chevelieri isolated from Lagerostromia tomentosa C. presl. The anticancer and antimicrobial activity of crude extracts, fractions and pure compounds were investigated as part of this study. Methods: An endophytic fungus (Aspergillus chevelieri) was isolated from the tissues of the stem of Lagerostromia tomentosa C. presl and identified through molecular biological procedure by DNA isolation, PCR, DNA sequencing and through searching the Gene Bank. Metabolomics profiling and dereplication studies were employed to choose the optimum growth medium and conditions that yield the most significant metabolites. The crude extract of the 30-days rice culture of Aspergillus chevelieri was subjected to bioactivity and metabolomics guided isolation approach. The structure of the isolated compounds was determined on the basis of 1D, 2D NMR and mass spectrometry (HR-ESIMS) analysis. Results: four bioactive fractions were further purified to produce five pure compounds, which are Ergosterol (1), Ergosterol peroxide (2), Campesterol (3), Flavoglaucin (4) and 3-O- methyl caffeic acid (5). Multivariate data analysis highlighted the most significant metabolites contributed to the bioactivity. Only 30 days RC extract of A. chevelieri was active among all fungal extracts. The pure compounds were tested for the anticancer and antimicrobial activity, compound (1) exhibited significant anti-trypanosomal activity, while compounds (2, 3, 4 and 5) effectively inhibited the growth of Escherichia coli, Staphylococcus aureus and Candida albicans. Conclusion: A combination of metabolomic- and bioassay-guided approaches gives an access to a shorter and faster route to highlight the active metabolites, which are highly correlated to the bioactivity during the first stage of fractionation.