Promise and pitfalls of acetogenic Clostridium species for hydrogen and carbon dioxide-driven gas fermentation

Gas fermentation using anaerobic acetogenic bacteria represents a promising carbon capture and utilization strategy for converting C1 gases into valuable bioproducts. Among acetogens, Clostridium species have attracted significant attention due to their ability to produce native C2–C6 acids and alcohols through their versatile metabolism. While industrial applications have primarily focused on CO- and syngas-based fermentation, a large fraction of anthropogenic emissions originates from industrial sectors generating CO 2 -rich gas streams with limited or negligible CO content. CO 2 - fermentation, powered by renewable H 2 , offers a potential route for the valorization of these emissions and the development of carbon-negative bioprocesses. However, research on CO 2 /H 2 -driven gas fermentation by Clostridial acetogens remains limited compared with CO- and syngas-based systems, and a comprehensive overview of their potential is still lacking. This mini-review summarizes the current state of research, highlighting the best laboratory-scale performances achieved for native product formation and discussing the key metabolic constraints affecting growth and productivity. Furthermore, it provides a framework for selecting suitable host species and operating conditions tailored to specific target molecules, while exploring recent advances in strain development and process optimization that may support the future scale-up of CO 2 /H 2 -driven gas fermentation and its application in sustainable biomanufacturing.