Systems biology and metabolic engineering for obtaining E. coli mutants capable to produce succinate from renewable resources

The bio-based conversion of glycerol and glucose to valuable chemicals, such as succinate, by commonly used microorganisms, like Escherichia coli is of major interest. The petrochemically based succinate production can be replaced by a new sustainable and environmental friendly one and the glycerol resulted from biodiesel industry can be therefore reused. Genetically engineered strains could be used to provide a cost-effective, ecologically sustainable alternative to the current petrochemical production process. Systems biology and in silico analyses are necessary to study complex biological systems and successfully apply metabolic engineering. Here, a systems biology approach through model-driven evaluation of the cell metabolism and the production potential of an important biochemical compound, under different environmental conditions is presented. To investigate the genetic and environmental perturbations, as well as the relationship between biomass and succinate yield, in silico metabolic analysis was carried out using constraint-based metabolic flux simulations. Different methods were used to design strains with increased capabilities to produce succinate. The study provided specific metabolic interventions that can be experimentally implemented, characterized the metabolic network and outlined a strain design pipeline that can be used to study complex biological systems and processes.