Production of novel fungal secondary metabolites by epigenetically activating the silent biosynthetic gene clusters.

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In this study, we found some effective conditions for activating fungal secondary metabolism by using epigenetic modifiers such as HADC and DNA methyltransferase inhibitors. Using the conditions, we successfully isolated structurally diverse novel fungal secondary metabolites from cryptic biosynthetic pathways, showing the utility to enlarge chemical space composed of natural products. In addition, we obtained the evidence that over expression of LaeA, an epigenetic enzyme, in fungi is possible way to enhance their production of secondary metabolites.