Efficient biosynthesis of 3-hydroxypropionic acid from ethanol in metabolically engineered Escherichia coli

Engineering microbial cell factories to convert CO₂-based feedstock into chemicals and fuels provide a feasible carbon–neutral route for the third-generation biorefineries. Ethanol became one of the major products of syngas fermentation by engineered acetogens. The key building block chemical 3-hydroxypropionic acid (3-HP) can be synthesized from ethanol by the malonyl-CoA pathway with CO₂ fixation. In this study, the effect of two ethanol consumption pathways on 3-HP synthesis were studied as well as the effect of TCA cycle, gluconeogenesis pathway, and transhydrogenase. And the 3-HP synthesis pathway was also optimized. The engineered strain synthesized 1.66 g/L of 3-HP with a yield of 0.24 g/g. Furthermore, the titer and the yield of 3-HP increased to 13.17 g/L and 0.57 g/g in the whole-cell biocatalysis system. This study indicated that ethanol as feedstock had the potential to synthesize 3-HP, which provided an alternative route for future biorefinery.