Spatiotemporal Decoupling of Carbon and Energy Flux Enables Efficient Biomanufacturing of Aviation Fuel Precursors from CO(2).

Sustainable biomanufacturing of high-value, structurally complex chemicals directly from CO represents a frontier for carbon neutrality yet remains fundamentally constrained by a trade-off intrinsic to photobiohybrid systems: catabolic oxidation of fixed carbon must be invoked to regenerate intracellular reducing power, creating a futile cycle that reoxidizes photosynthetically fixed carbon back to CO and erodes the overall carbon atom economy. Overcoming this bottleneck requires a unified platform capable of simultaneously supplying carbon substrates and regenerating reducing equivalents to maximize anabolic flux. Here, we report a spatiotemporally decoupled photobiohybrid system that achieves carbon-efficient CO conversion through an "extracellular fixation and intracellular empowerment" strategy. A bifunctional catalyst of iron single atoms anchored on nitrogen-doped carbon quantum dots (Fe-NC QDs), featuring atomically dispersed Fe-N active sites, was developed. Extracellularly, the Fe-NC QDs catalyze CO reduction to methanol with a production rate of 826.10 μmol·g·h and 91.33% selectivity; intracellularly, the same QDs are internalized by engineered and photocatalytically regenerate NADH through a flavin-mediated electron transport chain. Coupling this bifunctional catalyst with an artificial phosphoketolase pathway enables the direct conversion of CO into the C15 aviation fuel precursor epi-isozizaene at a titer of 1.98 mg·L, corresponding to a 3-fold increase in product titer over conventional methanol-feeding strategies. By spatiotemporally decoupling carbon supply from energy regeneration, this work establishes a generalizable framework for solar-driven biosynthesis of complex multicarbon feedstocks and advances the development of a circular bioeconomy.