ABSTRACT

Systems biology analyzes both the components and the interactions of organisms to understand their organization and to predict behavior.1,2 Currently, systems biology has a variety of applications using industrial organisms and in medical problems. This holistic approach involves a combination of modeling and omics analyses and was naturally more rapidly and easily applied to prokaryotic organisms. Nevertheless, fungal systems biology started as a discipline quite soon, especially driven by the accumulated knowledge in the yeast Saccharomyces cerevisiae that is, simultaneously, a eukaryotic model organism and a widely used industrial organism.3-5

Within systems biology, integrated studies of metabolism (metabolic systems biology) emerge for two main reasons: availability of data and importance of applications. Indeed, accumulated knowledge on metabolism is vast and allows creating reliable models that allow simulation of microorganism behavior in a variety of conditions. Also, metabolism is directly related to valuable end products and a variety of diseases have a metabolic origin.6,7 Knowledge on metabolism of a given organism is easily applied to other organisms, using simple bioinformatics tools such as the basic local alignment tool (BLAST),8 while the same is not true for other functions such as transcription regulation and signaling. Therefore, it is easy to understand why a variety of metabolic models are available for organisms ranging from simple bacteria to lamentous fungi or even

6.1 Motivation ...............................................................................................................................69 6.2 Metabolic Systems Biology .................................................................................................... 70 6.3 Functional Genomics .............................................................................................................. 71

6.3.1 Other Omics ................................................................................................................ 72 6.4 Genome-Scale Metabolic Models........................................................................................... 73

6.4.1 Genome Annotation .................................................................................................... 76 6.4.2 Assembling the Metabolic Network ...........................................................................77