Engineering a solar formic acid/pentose (SFAP) pathway in Escherichia coli for lactic acid production

Microbial CO₂ fixation into lactic acid (LA) is an important approach for low-carbon biomanufacturing. Engineering microbes to utilize CO₂ and sugar as co-substrates can create efficient pathways through input of moderate reducing power to drive CO₂ fixation into product. However, to achieve complete conservation of organic carbon, how to engineer the CO₂-fixing modules compatible with native central metabolism and merge the processes for improving bioproduction of LA is a big challenge. In this study, we designed and constructed a solar formic acid/pentose (SFAP) pathway in Escherichia coli, which enabled CO₂ fixation merging into sugar catabolism to produce LA. In the SFAP pathway, adequate reducing equivalents from formate oxidation drive glucose metabolism shifting from glycolysis to the pentose phosphate pathway. The Rubisco-based CO₂ fixation and sequential reduction of C3 intermediates are conducted to produce LA stoichiometrically. CO₂ fixation theoretically can bring a 20% increase of LA production compared with sole glucose feedstock. This SFAP pathway in the integration of photoelectrochemical cell and an engineered Escherichia coli opens an efficient way for fixing CO₂ into value-added bioproducts.