A Multiobjective Strain Design Platform for Modular Cell Engineering

Metabolic engineering has enabled the use of microbial cell factories for industrial production of biochemicals. However, developing an optimal strain for synthesis of one product with the conventional strategy is laborious and expensive. To accelerate and reduce the cost of strain engineering, we formulate the modular cell (MODCELL) design principles by exploiting the modular organization of metabolic networks and combinatorial possibilities of metabolic modules that enable the synthesis of a large space of biochemicals. Using multiobjective optimization methods, we develop novel algorithms to implement the MODCELL design for genome-scale metabolic networks and the associated software ModCell2.0. We demonstrate ModCell2.0 for design, construction, and validation of an E. coli modular cell for combinatorial synthesis of biochemicals, e.g., alcohols and bioesters from fermentable sugars and organic wastes. We envision MODCELL will provide a useful platform for modular cell engineering.