Improved production of 3-hydroxypropionic acid in engineered Escherichia coli by rebalancing heterologous and endogenous synthetic pathways.

To improve 3-hydroxypropionic acid (3-HP) production by Escherichia coli, glycerol accumulation needs to be reduced. To accomplish this, we constructed a novel E. coli strain that overexpresses the endogenous aldehyde dehydrogenase gene (puuC) under the control of a strong promoter. The fermentation performance of the engineered strain was significantly improved compared to that of the parental control strain in the presence of glucose and xylose. We also inactivated the puu operon repressor gene, puuR, which resulted in a decrease in glycerol accumulation and an increase in 3-HP production through the co-fermentation of glucose and xylose. Through fed-batch fermentation by utilizing glucose and xylose, the engineered strain, JHS_Δgypr-PT7, produced 53.7 g/L 3-HP and accumulated 1.5 g/L glycerol. This combination strategy, wherein we overexpressed the endogenous puuC gene from a strong promoter and eliminate its transcriptional repression, may be extended to rebalance another biochemical pathway.