Enhanced growth of 1-butanol producing Escherichia coli via a metabolic buffer

1-Butanol is a C4 aliphatic alcohol that is widely used as a gasoline blendstock. In this study, we report an underexplored metabolic route for the de novo biosynthesis of 1-butanol in Escherichia coli. Specifically, the 1-butanol biosynthetic pathway comprises a redesigned Clostridium-derived pathway for butyryl-CoA synthesis, followed by a CoA-acylating aldehyde dehydrogenase (PduP from Salmonella enterica) and an endogenous alcohol dehydrogenase (YqhD from E. coli). We found that abolishing thioesterases to block the formation of butyrate byproduct would lead to deleterious effects on the cell growth. Upon introducing a metabolic buffering pathway towards polyhydroxyalkanoate biosynthesis, the toxicity caused by metabolic imbalance was alleviated, accompanied by enhanced cell growth and 1-butanol productivity. A similar strategy was also validated to be effective for improving the production of hexane-2,3-diol, a potential cosmetic component with high value. In summary, this work successfully demonstrates that the metabolic buffering strategy exerts a synergistic effect on enhancing biochemical production with improved carbon recovery efficiency.