SYSTEMS BIOLOGY Constraint - Based Modeling of Metabolic Networks

Systems Biology is a powerful tool widely used to analyze in silico complex biological systems and subsystems, to understand the cellular behavior at the system-level; what kind of interactions are between cellular components and how are these networks organized and reorganized under different pressures, such as harsh environmental conditions, culture medium and even genetic modifications. In the present study the applications of constraint-based metabolic models and systems biology in metabolic engineering are discussed. Using these approaches the production potential of succinic acid from renewable resources (glucose or glycerol in minimal media) in Escherichia coli is analyzed. Simulations are made to determine which competitive pathways should be modified to reroute the carbon flux toward succinic acid and to determine the environmental conditions and metabolic engineering effects on cell metabolism. During the experiments different in silico and in vivo methods have been implemented to model, analyze, optimize and predict the metabolic behavior of E. coli.