Design frameworks for engineering efficient cell factory performance within host and industrial constraints

This talk will be given online.

Abstract:

Synthetic biology and microbial biotechnology offer sustainable routes to the manufacture of commodity and high value chemicals from agricultural by-products instead of petrochemical feedstocks. However, engineered gene circuits and metabolic pathways both co-opt the cell’s gene expression machinery for protein/enzyme production and divert metabolic flux away from key host biosynthetic building blocks to a desired product. These interactions impair host growth and complicate the engineering of synthetic functions. To overcome these difficulties, we propose a host-aware engineering approach which accounts for these constraints during the circuit/pathway design process. Here we present a dynamic whole cell modelling framework of microbial growth, metabolism, and gene expression which captures key host-circuit/pathway interactions. By coupling our modelling framework with systems engineering approaches and multi-objective optimization tools, we identify key design trade-offs, make recommendations for optimal host resource usage, and develop feedback control strategies which improve pathway productivity and yields.