Epigenetic Modification: A Key Tool for Secondary Metabolite Production in Microorganisms

Microorganisms are stupendous source of secondary metabolites, having significant pharmaceutical and industrial importance. Genome mining has led to the detection of several cryptic metabolic pathways in the natural producer of secondary metabolites (SMs) such as actinobacteria and fungi. Production of these bioactive compounds in considerable amount is, however, somewhat challenging. This led to the search of using epigenetics as a key mechanism to alter the expression of genes that encode the SMs toward higher production in microorganisms. Epigenetics is defined as any heritable change without involving the changes in the underlying DNA sequences. Epigenetic modifications include chromatin remodeling by histone posttranslational modifications, DNA methylation, and RNA interference. Biosynthetic gene cluster for SMs remains in heterochromatin state in which the transcription of constitutive gene is regulated by epigenetic modification. Therefore, small-molecule epigenetic modifiers, which promote changes in the structure of chromatin, could control the expression of silent genes and may be rationally employed for discovery of novel bioactive compounds. This review article focuses on the types of epigenetic modifications and their impact on gene expression for enhancement of SM production in microorganisms.