Continuous Valorization of Carbon Dioxide into the Fine Chemical Ectoine by <i>Hydrogenovibrio marinus</i>: A New Strategy for Pharmaceutical Production

Current challenges in biopharmaceutical manufacturing, such as ectoine production, include high operational costs and limited availability. Transitioning to processes that valorize renewable carbon sources like CO₂ into ectoine can make production more sustainable and accessible to the economy and society. However, cell platforms that produce ectoine with CO₂ still require bioprocess optimization and resilient microorganisms able to continuously maintain high ectoine yields and CO₂ removals. A comprehensive screening of cultivation and operational strategies was conducted in six stirred-tank gas bioreactors using the strain <i>Hydrogenovibrio marinus</i>, a halophilic, fast-growing, hydrogenotrophic bacterium with low nutrient requirements. Gas residence times of 120 min at gas ratios of 10:40:50 CO₂:H₂:air (% v/v) and dilution rates of 0.25 d^-1 boosted ectoine production and biomass growth during long-term operation. Under these conditions, ectoine productivity reached 5.0 ± 0.3 g m^-3 d^-1, with maximum specific ectoine contents of 134.0 ± 6.3 mg_Ect g_biomass^-1, achieving yields similar to heterotrophic strains. This study demonstrates for the first time the feasibility of integrating ectoine production with continuous CO₂ abatement using H₂ as a clean and hazard-free energy source, which marks a significant advancement in sustainable ectoine manufacturing and CO₂ circularity.