Redirecting carbon to bioproduction via a growth arrest switch in a sucrose-secreting cyanobacterium

Cyanobacteria are microbes with high photosynthetic efficiencies, making them a promising target for the production of sustainable bioproducts directly from solar energy and carbon dioxide. The most common efforts to increase cyanobacterial bioproduction involve diverting cellular resources away from cellular biomass and towards a heterologous pathway, for example through nutrient starvation or knockout of genes in competing metabolic pathways. Here we show that an inducible cell growth arrest switch can be used to increase the partitioning of carbon to an engineered sucrose sink. Specifically, we show that overexpression of Regulator of Phycobilisome-Associated B (RpaB), an essential response regulator in Synechococccous elongatus PCC 7942, allows for inducible arrest of cell growth and is associated with a > 2-fold higher specific productivity of a heterologous sucrose secretion pathway. Finally, we show that sucrose export can partially relieve photosynthetic feedback inhibition imposed by the RpaB dependent growth arrest, allowing sucrose-secreting strains to maintain higher photosynthetic efficiencies. This work provides a novel conceptual framework for improving photosynthetic productivity and cyanobacterial bioproduction.