(281a) Design of Modular Cells By Goal Attainment Optimization

Goal attainment optimization is a mathematical framework to describe the simultaneous optimization of conflicting objectives that must all reach a performance above a threshold or goal. In this study, we use goal attainment optimization to design modular cells that can couple with various modules, where each goal corresponds to the minimum design requirements (i.e., yields and rates) of a target product. This modular design approach aims to overcome the prohibitively slow and difficult strain design process to enable a broader industrial application of whole-cell biocatalysis to produce fuels, chemicals, and therapeutics. Using a genome scale metabolic network model of Escherichia coli, we demonstrate that 20 biochemically diverse products can be effectively synthesized at high yields and rates by a modular cell with only a few genetic manipulations. Flux analysis reveals this broad modularity phenotype is supported by the natural modularity of core metabolic pathways. We envision this modular design framework can be applied for other synthetic biology applications such as design of modular bioremediation and biosensor cells.