Transcription Factor Engineering in <i>Aspergillus\nnidulans</i> Leads to the Discovery of an Orsellinaldehyde Derivative\nProduced via an Unlinked Polyketide Synthase Gene

Secondary\nmetabolites are generally produced by enzymes encoded\nby genes within a biosynthetic gene cluster. Transcription factor\ngenes are frequently located within these gene clusters. These transcription\nfactors often drive expression of the other genes of the biosynthetic\ngene cluster, and overexpression of the transcription factor provides\na facile approach to express all genes within a gene cluster, resulting\nin production of downstream metabolite(s). Unfortunately this approach\nis not always successful, leading us to engineer more effective hybrid\ntranscription factors. Herein, we attempted to activate a putative\ncryptic biosynthetic gene cluster in <i>Aspergillus nidulans</i> using a combination of transcription factor engineering and overexpression\napproaches. This resulted in the discovery of a novel secondary metabolite\nwe term triorsellinaldehyde. Surprisingly, deletion of the polyketide\nsynthase gene within the gene cluster did not prevent triorsellinaldehyde\nproduction. However, targeted deletion of a polyketide synthase gene\nelsewhere in the genome revealed its role in triorsellinaldehyde biosynthesis.