Systems Biology of Glucose Sensing and Repression in Aspergillus niger: Lessons from Genomics and Transcriptomics

Doctoral thesis, 2010

Aspergillus comprises a genus of multicellular eukaryotic microorganisms containing close to 200 different species. Among them, the filamentous fungus Aspergillus niger exhibits great diversity in its phenotype and it is found, both in marine and terrestrial habitats. A. niger produces many metabolites that are valuable commodities, e.g., organic acids, but is also able to secrete a wide range of hydrolytic enzymes, while some strains exhibit pathogenicity. Although A. niger is a widely used industrial species used for metabolite production, relatively little is known about the regulation of its metabolism. We therefore undertook a functional genomics approach to produce transcriptome data of high quality trying to uncover novel regulatory processes and the transcription factors associated to them. Throughout this thesis we worked with several wild type and gene deletion A. niger strains, i.e., the ancestor of an industrial glucoamylase producer strain, A. niger BO1; the acidogenic wild type strain ATCC 1015 and the industrial enzyme-producing strain CBS 513.88, both strains already sequenced. High variation within these two later strains was confirmed with the genomics and transcriptomics approaches used in combination with exo-metabolite profiling. Genotypic differences were observed to accumulate in metabolic pathways, e.g., essential to production of organic acids for A. niger ATCC 1015 and of protein synthesis for CBS 513.88. Overall, the studies reported in this thesis illustrate the complexity of the regulatory circuits regulating cellular processes. For example, through comparative genomics approaches, we exposed the reasons why glycerol metabolism and maltose metabolism are different in closely related species. We demonstrated that the two industrially relevant Aspergillus species, A. niger and A. oryzae do not possess the same maltose uptake, metabolism and regulatory mechanisms. While, the two later studies reported in this thesis were not as focused as the previous ones, but more exploratory in terms of looking for novel regulatory roles played by the transcription factors studied: AdrA, FacB, CreA and AreB; we think that our results could help to improve understanding of the metabolic regulation in A. niger by several transcriptional regulators that will lead to better tuning and improvement of production processes and wider exploitation of A. niger as a cell factory.