Natural product search is an enduring revitalization upon the exploration of a huge already exotic potential for Secondary Metabolite (SM) production obscure in microbial genomes.

Filamentous fungi genomes have an immense number of “orphan” SM gene clusters. Current evaluation indicates that only 5% of extant fungal species have been explored, thus the apparent for the disclosure of novel metabolites in fungi is extensive. In this situation, fungi burgeoning in severe environments are of special interest since they are distinguished producers of astonishing chemical structures. Genome mining strategies, more specifically epigenetic strategies are playing an important role in natural product discovery. This review has been organized and written to focus on available epigenetic approaches, targeting on DNA methyltransferase and histone deacetylase inhibitors along with reported novel secondary metabolites. To the best of our knowledge, this review article is the first attempt to incorporate the facts regarding DNA methyltransferase inhibitors and histone deacetylase inhibitors along with reported novel secondary metabolites with their recorded bioactivities.