Systematic over-expression of secondary metabolism transcription factors to reveal the pharmaceutical potential of Aspergillus nidulans

Many life-saving drugs are derived from fungal secondary metabolites, and the rich diversity of these metabolites is a gold mine of bioactive compounds for drug discovery. However, the biosynthetic genes for most secondary metabolites remain transcriptionally silent in fungi, posing a significant bottleneck in their discovery. Here, we apply a systematic approach to separately over-express 51 secondary metabolism-related transcription factors using the strong inducible promoter of the xylP gene from Penicillium chrysogenum. Growing the individual secondary metabolism transcription factor over-expression strains under inducible conditions leads to the production of a collection of diverse metabolites with anti-bacterial, anti-fungal and anti-cancer activities. The overall approach and the over-expression system established in this study are broadly-applicable, providing a valuable means to revealing the pharmaceutical potentials of fungi.