Systems Approaches for Exploring and Exploiting Cellular Metabolism View Edit Track

Genome-scale networks of metabolism and regulation can be reconstructed from an organism’s genome annotation. Models generated from these reconstructions can be used to integrate and analyze different types of experimental data in order to generate hypotheses about biochemical network structure, interactions between organisms and their environments, and responses to genetic and environmental perturbations. Examples from modeling different bacteria with biotechnology and metabolic engineering applications will be presented to illustrate how modeling and experimental efforts can be combined to improve computational models and our understanding of cellular metabolism and regulation. Once accurate models are developed, computational tools can be applied to design microbial strains with enhanced chemical production. We have recently developed new methods for proposing metabolic engineering strategies based on metabolic and regulatory model predictions. These strategies can involve transcription factor and metabolic gene deletions, as well as enzyme over expression. Using these approaches we have identified genetic strategies for improving production of a variety of biochemicals in E. coli including ethanol, isobutanol, succinate, amino acids, and malate.