Gas-Phase Integration of Trophically Distinct Microbial Cultures for Net-Reduced CO2 and Enhanced Metabolite Production.

The continued increase in atmospheric CO2 concentrations has intensified global efforts to develop sustainable biotechnologies that capture and reutilise carbon rather than releasing it. While photosynthetic microorganisms provide a renewable route for CO2 fixation into organic products, heterotrophic fermentation remains the industrial standard due to its high productivity, controllability and scalability. Consequently, integrating the carbon efficiency of autotrophic processes with the productivity of heterotrophic systems may represent a promising strategy toward circular biomanufacturing. Here, we developed a gas-linked co-culture system designed to spatially separate heterotrophic and autotrophic metabolisms while enabling gas-phase CO2 exchange between them. This configuration allowed CO2 released during heterotrophic metabolism to be reutilised in autotrophic metabolism, supporting cooperative carbon cycling. Compared to non-linked controls, the gas-linked system enhanced biomass accumulation and nearly doubled the production of value-added metabolites-namely polyhydroxybutyrate (PHB) and carotenoids-while reducing net CO2 emissions by 20.62%. Although further optimisation is necessary to approach a fully net-zero process, this study demonstrates that gas-phase integration of trophically distinct cultures offers a promising platform for circular carbon biorefineries.