Engineering Escherichia coli lifespan for enhancing chemical production

Industrial chemical production from renewable feedstocks by microbial cell factories provides a promising avenue towards sustainability. However, the small size of bacterial cells and environmental stress significantly affect microbial cell factory performance. Here, we engineered the Escherichia coli lifespan to improve the chemical production of poly(lactate-co-3-hydroxybutyrate) and butyrate. The replicative lifespan was shortened by deleting a carbon storage regulator, and the chronological lifespan was extended by deleting a response regulator and overexpressing sigma-38 in Escherichia coli. The replicative lifespan was fine-tuned using a two-output recombinase-based state machine, and the cell size was enlarged 13.4-fold. The highest poly(lactate-co-3-hydroxybutyrate) content of 52 wt% was achieved in a 5-l fermenter. The chronological lifespan was modulated through a multi-output recombinase-based state machine, resulting in the highest butyrate titre of 29.8 g l(-1), by programming cell differentiation according to different fermentation stages. These results highlight the applicability of engineering the bacterial lifespan to increase microbial cell factory performance.