Epigenetic Regulation of Fungal Secondary Metabolites for the Enhancement of Therapeutically Active Compounds

The microbial flora has always been a center of interest for the identification of novel bioactive secondary metabolites (SMs) used against a diversity of infections and ailments. These bioactive compounds are produced by the hosts in response to different stress conditions. Novobiocin naturally synthesized in Streptomyces spheroids, Echinocandin B from Emericella rugulosa, Penicillin from Penicillium chrysogenum, and Gentamycin from Micromonospora purpurea are such examples. In nature, the secondary metabolites genes, either cryptic or microbial bioactive compounds, synthesize in trace amounts under specific environmental conditions, physiological conditions which make their bioavailability scarcer. Different strategies such as induced stress stimuli, cloning the genes under the control of strong promoters, downregulating the expression of negative regulators, epigenetic manipulations, etc. have been tried to increase SM bioavailability. The posttranslational modifications of histones proteins render to regulate the secondary metabolites and have also been implied. Here, in this chapter, we emphasized the epigenetic regulation for enhancement of the production of therapeutically significant bioactive compounds in fungi. DNA wrapped around the histones proteins undergo different posttranslational modifications that facilitate chromatin DNA packaging around the histones proteins either loose (euchromatin) or tight (heterochromatin). Such alterations in the histones proteins epigenetically modulate the expression of genes that are responsible for regulating different metabolic events. Relevance of different epigenetic approaches such as the use of Histone deacetylase inhibitors (HDACs) or DNA methyl transferase inhibitors (DNMTs) concern different fungal bioactive compounds. These modifications could be intrinsically programmed or affected externally. Different studies have provided supportive arguments about the use of epigenetic modifiers for increasing the bioavailability of different fungal bioactive compounds. These epigenetic modifiers either act locally or globally for inducing or repressing the secondary metabolites synthesis genes. Different epigenetic modifiers have been earlier studied for the modulation of secondary metabolite synthesis in fungi. For instance, 5-azacytidine, hydralazine hydrochloride, trichostatin A, trapoxin B, etc. The chapter elaborates on a more developed understanding of histone modifiers for activation/induction of secondary metabolites yield of pharmacologically significant fungal-derived bioactive compounds.