De novo artificial synthesis of hexoses from carbon dioxide

Developing artificial "CO₂-sugar" platforms is meaningful for addressing challenges posed by land scarcity and climate change to the supply of dietary sugar. However, upcycling CO₂ into complex polyoxygenated carbohydrates involves several major challenges, including achieving enantioselective and thermodynamically driven transformation and expanding product repertoires while reducing energy consumption. We present a versatile chemoenzymatic roadmap based on aldol condensation, iso/epimerization, and dephosphorylation reactions for asymmetric CO₂ and H₂ assembly into sugars with perfect stereocontrol. In particular, we developed a minimum ATP consumption and the shortest pathway for bottom-up biosynthesis of the fundamental precursor, fructose-6-phosphate, which is valuable for synthesizing structure-diverse sugars and derivatives. Engineering bottleneck-associated enzyme catalysts aided in the thermodynamically driven synthesis of several energy-dense and functional hexoses, such as glucose and D-allulose, featuring higher titer (63 mmol L^-1) and CO₂-product conversion rates (25 mmol C L^-1 h^-1) compared to established in vitro CO₂-fixing pathways. This chemical-biological platform demonstrated greater carbon conversion yield than the conventional "CO₂-bioresource-sugar" process and could be easily extended to precisely synthesize other high-order sugars from CO₂.