Fig. 1

Schematic representation of the main mass and energy balances involved in biomass formation, along with alternative metabolic engineering strategies to make target compounds. a Target product formation is metabolically engineered using classical approaches that redirect native fluxes toward it. Product formation and biomass formation compete for carbon and energy, which eventually leads to strain instability. b Overview of growth-coupled metabolic engineering strategies. Others have proposed to tie fluxes to biomass and target product by linking energy and/or redox regeneration to product formation (blue). We propose here to achieve this by knocking out the genes encoding pathways responsible for re-utilizing the side products of anabolism (green)