SYSBIOMICS of Aspergilli: SYStems Biology, BIoinformatics and OMICS analysis of Aspergilli cell factories

Abstract: Aspergilli represent a group of filamentous fungi that plays a key role in industrial biotechnology, and as human, animal and plant pathogens. Here three Aspergillus species, namely Aspergillus oryzae, Aspergillus niger and Aspergillus nidulans are considered. These three species serve as working horses in industrial production of enzymes and chemicals and as key models for basic scientific work. Due to their wide applications, it is valuable to gain understanding of their metabolism, regulation and evolution with respect to genotypes and phenotypes, as this may lead to improved industrial fermentation processes for desired product formation (e.g. enzymes). We therefore applied three approaches for this investigation, namely SYStems biology, BIoinformatics and OMICS analysis (SYSBIOMICS). Firstly, we developed BIoinformatics methods to improve the genome annotation of A. oryzae and this improved annotation was used to reconstruct a high quality genome-scale metabolic network that could be used for mathematical modeling of the physiology and for OMICS data integration, which are the core of SYStems biology. Secondly, we designed a tri-Aspergillus DNA microarray chip to monitor the global regulation response at the transcriptional level. This DNA chip has been exploited to reveal conserved regulatory responses through evolution in the three aspergilli in response to change in carbon source. This resulted in mapping of key regulatory points of metabolism in these fungi, and it showed that SYSBIOMICS analysis of transcriptional data can lead to reconstruction of how carbon metabolism is regulated. Lastly, we also applied the SYSBIOMICS concept to identify possible key players/targets associated with protein production in a high producing strain of A. oryzae. This analysis may enable diagnosis and improvement of industrial process of protein production. In conclusion, through a number of studies, it has been demonstrated in this thesis that SYSBIOMICS can find wide applications in industrial biotechnology and assist in improving industrial process required for sustainable production of enzymes and chemicals in the future.