Fungi produce a broad range of secondary metabolites with various bioactivities that have allowed them to be used as antibiotics and pharmaceutical drugs. The genes encoding secondary metabolites are commonly organized contiguously into biosynthetic gene clusters. The close spacing of functionally related genes facilitates the identification of multiple parts of a secondary metabolite pathway, its regulation, and provides the possibility of discovering novel bioactive compounds.
However, (i) the function of each genes within biosynthetic gene cluster is often not well defined, (ii) the regulation of gene clusters is very complex and, so far, remains mostly uncharacterized.
Herein, three Aspergillus niger gene clusters were investigated. The transcriptional regulation of two clusters thought to be involved in malformins production and one unknown cluster not associated with any metabolites, was studied. The overexpression of transcription factors and knocked out of backbone enzymes were done by gene replacement. The production of malformins and others secondary metabolites was assessed by comparative metabolomics and transcriptomics using mass spectrometry and RNA-sequencing, respectively.