A major challenge in carbon-based bioproduction is achieving high-yield conversion of carbon feedstocks—such as methanol—into target compounds, while avoiding carbon losses to biomass or CO2 emissions. Current microbial metabolism prioritizes energy and biomass generation, often oxidizing a substantial fraction of carbon as CO2 via respiration, limiting the sustainability of bio-based production systems. CarboNcare proposes a breakthrough solution: a synthetic fermentative metabolism engineered into E. coli and P. putida, which forces methanol assimilation into value-added products without releasing CO2. These strains grow only if they convert methanol into target chemicals, lactate, succinate, and 2,3-butanediol with high stoichiometric yields, ensuring a tight growth-product coupling and preventing evolutionary drift toward biomass overproduction. By bypassing oxidative respiration and instead generating energy through substrate-level phosphorylation and controlled electron transfer to quinones, CarboNcare eliminates the need for CO2-emitting pathways. Electrons are redirected to internal metabolites (e.g. pyruvate, acetyl-CoA), maximizing carbon retention in final products. The system operates under aerobic but non-respiratory conditions, simplifying scale-up, reducing methanol loss, and enhancing process robustness. CarboNcare follows a Design-Build-Test-Learn (DBTL) approach, combining cutting-edge strain design with metabolic rewiring. The project brings together leading European partners: CHA (strain engineering and synthetic metabolism), DTU (systems biology and P. putida engineering), MPI (computational modelling), ULEI (enzyme engineering), CEA (adaptive laboratory evolution), IN and DEC (communication, stakeholder engagement, business modelling), and HES-SO (bioprocess development and scale-up). Together, they will deliver a robust and climate-resilient platform for sustainable methanol-based bioproduction.