Studies on the antifungal and serotonin receptor agonist activities of the secondary metabolites from piezotolerant deep-sea fungus Ascotricha sp.

The potent antifungal agent sesquiterpenes and serotonin 5-HT2C agonist ascotricin were produced by a newly isolated deep-sea fungus Ascotricha sp. This fungus was isolated from deep-sea sediment collected at a depth of 1235 m and characterized. Piezotolerance was successfully tested under high pressure-low temperature (100 bar pressure and 20oC) microbial cultivation system. Production of secondary metabolites was enhanced at optimized culture conditions. The in-vivo antifungal activity of sesquiterpenes was studied using the Caenorhabditis elegans - Candida albicans model system. The sesquiterpenes affected the virulence of C. albicans and prolonged the life of the host C. elegans. These findings suggest that sesquiterpenes are attractive antifungal drug candidates. The 5-HT2C receptor agonist is a potential target for the development of drugs for a range of central nervous system disorders. The interaction of 5-HT2C agonist ascotricin with the receptor was studied through bioinformatic analysis. The in silico molecular docking and molecular dynamic simulation studies demonstrated that they fit into the serotonin 5-HT2C active site and the crucial amino acid residues involved in the interactions were identified. To our knowledge, this is first report of in vivo antifungal analysis of sesquiterpenes and in silico studies of serotonin 5-HT2C receptor-ascotricin complex.