Investigation of anticancer compounds in the natural productome of marine algae associated endophytic fungi

Abstract

Cancer is one of the leading causes of death worldwide. Owing to the complex ways in which this disease develops, there is a constant demand for new drugs. Natural products have delivered great promise in inspiring chemotherapy, for example, Taxol, Trabectedin, Plinabulin, Marizomib, Midostaurin, etc. Endophytic fungi have potentiated this promise by producing potent bioactive compounds. They live symbiotically in the internal tissues of higher organisms. Marine endophytic fungi offer a diverse chemical space for the discovery of novel anticancer compounds, sustainably. Marine endophytes demonstrate a higher chemical diversity, possibly due to immense competition and abiotic and biotic stress. These secondary metabolites are highly potent at minuscule concentrations because they act in dilute environments over larger distances. In this study, 26 endophytic fungi were isolated and identified from 10 marine algal samples collected from the Konkan coast, India. This work led to the first diversity study of marine algae-associated endophytic fungi of the Konkan coast. All the fungal extracts were screened for cytotoxicity on several human cancer cell lines, A431, HeLa, A549 and MCH-7. Three endophytic fungi, Aspergillus unguis AG 1.1 (G), Chaetomium globosum PG 1.6, and Aspergillus unguis AG 1.2, were chosen for further study as their IC50 values were lt 10 and#956;g/mL. Chrysin, a dihydroxyflavone was purified and reported for the first time from a marine endophyte C. globosum. It was so far known to be found in honey and passionflower. It induced apoptosis, G1 phase cell cycle arrest, MMP loss, and ROS production in MCF-7 cells. Further, using metabolic profiling of C. globosum, several key intermediates of the chrysin biosynthesis pathway were identified, thus, proving the presence of flavonoid biosynthetic machinery in the marine fungus. The yield of chrysin was enhanced using optimization of several media and fermentation parameters, inducing abiotic and biotic stresses and elicitation. The free use of chrysin in clinic