In silico Design of a Phenotype Switch for Cell Factories

Synthesis of high-value biochemicals such as terpenoids and fatty acid derivatives competes severely with cell growth. Yet, sufficient biomass is required for feasible volumetric production rates and final titer in reasonable cultivation times. Thus, we are interested in developing cell factories with a capability to switch phenotype from fast growth to optimized production during a production process. Here we present a novel computational method to identify a minimal target set of endogenous reactions to be placed under synthetic dynamic regulation to switch the cellular phenotype. We have identified the minimal target sets for 29 products, both native and heterologous, in Saccharomyces cerevisiae. We enumerated alternative solutions to apply heuristics for the creation of final designs. We further propose modularization to speed up cell factory development and used a genetic algorithm to create a modularized chassis design with minimal total number of modifications for the set of products.