Rational Design of Modular Cells for Efficient Combinatorial Biosynthesis of Designer Bioesters

In the conventional strain engineering approach, relevant hosts such as Escherichia coli and Saccharomyces cerevesiae are commonly engineered and optimized to produce target products with different genetic modifications. An engineered host that is optimized to produce one target product may not be suitable to function as an optimal host to efficiently produce other target compounds, which makes the conventional approach laborious and expensive. To address this bottleneck, we are developing a novel MODCEL (Modular Cell) toolbox based on the metabolic network modeling to design modular cells that can metabolically couple with a diverse class of chemicals- and biofuels-producing pathways as exchangeable production modules to efficiently produce a diverse combinatorial set of chemicals and biofuels. We will present the design, construction, and characterization of optimal modular E. coli cell factories assembled from an optimal modular cell and exchangeable production modules in a rapid plug-and-play fashion to produce a diverse combinatorial spectrum of bioesters that can be used as fragrances, flavors, solvents, and biodiesels.