Overexpression of an LaeA-like Methyltransferase Upregulates Secondary Metabolite Production in .

Fungal secondary metabolites (SMs) include medically valuable compounds as well as compounds that are toxic, carcinogenic, and/or contributors to fungal pathogenesis. It is consequently important to understand the regulation of fungal secondary metabolism. McrA is a recently discovered transcription factor that negatively regulates fungal secondary metabolism. Deletion of (Δ), the gene encoding McrA, results in upregulation of many SMs and alters the expression of more than 1000 genes. One gene strongly upregulated by the deletion of is , a putative methyl transferase related to LaeA, a major regulator of secondary metabolism. We artificially upregulated by replacing its promoter with strong constitutive promoters in strains carrying either wild-type or Δ. Upregulation of on various media resulted in increased production of the important toxin sterigmatocystin and compounds from at least six major SM pathways. is, thus, a master SM regulator. Δ generally resulted in greater upregulation of SMs than upregulation of , indicating that the full effects of on secondary metabolism involve genes in addition to . However, the combination of Δ and upregulation of generally resulted in greater compound production than Δ alone (in one case more than 460 times greater than the control). This result indicates that deletion of and/or upregulation of can likely be combined with other strategies for eliciting SM production to greater levels than can be obtained with any single strategy.