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 CO2-rich gas streams with limited or negligible CO content. CO2- fermentation, powered by renewable H2, offers a potential route for the valorization of these emissions and the development of carbon-negative bioprocesses. However, research on CO2/H2-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 CO2/H2-driven gas fermentation and its application in sustainable biomanufacturing.