| Filamentous fungi produce numerous small molecules with biological activities. These molecules, known as secondary metabolites, are produced by clustered genes located adjacent to one another in the genome. It is hypothesized that one method of coregulating these genes is through the modification of chromatin structure. Here, we examine the ability of increasing histone acetylation marks to activate known secondary metabolite clusters, discover unknown compounds, and to further our knowledge about previously uncharacterized clusters. We identify that overexpression of the acetyltransferase EsaA leads to increased acetylation of histone 4 lysine 12, which leads activation of normally produced metabolites, including sterigmatocystin and penicillin. In the following chapters, we utilize a strain deficient for the histone deacetylase RpdA, and use both global metabolomics and targeted approaches to identify a family of novel compounds, the deusamides. Finally, two previously uncharacterized secondary metabolite clusters are activated and characterized. |
