S75: Using computations to reconstruct and redirect metabolism

Metabolism is defined as the full complement of chemical transformations in living systems. Systems biology techniques are increasingly being used to elucidate and quantify the full range of molecules (e.g., metabolite concentrations) and transformations (e.g., reaction fluxes) at work. In this talk, we will discuss how we can speed up the process of building organism-specific metabolic models by standardizing reaction entries, automatically filling-in connectivity gaps and restoring consistency with gene essentiality experiments. We will highlight ongoing genome-scale microbial, archaeal and plant reconstruction efforts in our group and explore how computations can help elucidate metabolic flows using isotope labeling experiments. The latest techniques will also be described for exhaustively identifying all paths that connect a source to a target metabolite (using a k-shortest path algorithm) followed by the identification of all genetic manipulations (using OptForce) leading to the microbial overproduction of targeted compounds including chemicals identified as promising biofuels.