Design, Construction, and Validation of Modular Chassis Cells for Efficient Combinatorial Biosynthesis of Chemicals

Transforming biology into engineering practice has a great potential to shape the industrialization of biology that will drive rapid development of novel microbial manufacturing platforms. These platforms will be capable of producing a vast number of industrially relevant chemicals at scale from alternative renewable feedstocks or wastes (e.g., biomass residues, biogas methane, syngas, CO2) without harming the environment. The challenge is to develop novel microbial manufacturing platforms to produce targeted chemicals with high efficiency in a rapid, predictable, and reproducible fashion. The conventional approach involves engineering each desirable cell in many trial-and-error optimization cycles. To engineer new desirable cells to produce other target chemicals, the entire process must be repeated, which is laborious and expensive. To address these bottlenecks, we have developed the MODCELL (Modular Cell) tool to design modular cells that can metabolically and genetically couple with a diverse class of exchangeable production modules for combinatorial biosynthesis of novel chemicals in a plug-and-play fashion requiring minimum iterative strain optimization cycles. We will present the design, construction, and validation of an E. coli modular cell for a combinatorial biosynthesis of novel bioesters that can be used as fragrances, flavors, solvents, and biodiesels from biomass-derived sugars and waste streams.