Metabolism and engineering of chemolithoautotrophic bacteria for carbon dioxide fixation

Chemolithoautotrophic bacteria represent a diverse group of microorganisms capable of utilising carbon dioxide (CO₂) as their sole carbon source, deriving the necessary energy for growth and metabolism from redox reactions involving inorganic compounds such as hydrogen, sulfur, or iron. These organisms have attracted substantial scientific and industrial interest due to their dual potential to function as biological CO₂ sinks, mitigating greenhouse gas accumulation, and as microbial platforms for the sustainable biosynthesis of value-added compounds. Their natural CO₂ fixation pathways, including the Calvin-Benson-Bassham cycle, the reductive tricarboxylic acid cycle, the Wood-Ljungdahl pathway, 3-hydroxypropionate bi-cycle, and reductive glycine pathway constitute the biological foundation for carbon assimilation in these organisms. However, these native pathways often exhibit limited efficiency, constraining their broader application. This comprehensive review discusses recent advances and opportunities in the optimization and redesign of CO₂ fixation networks in chemolithoautotrophic bacteria. It extends to the design and development of novel, energy-efficient routes for CO₂ fixation, which hold significant potential for large-scale implementation aimed at mitigating greenhouse gas emissions. In addition, the review assesses energy generation and utilization within carbon fixation networks, as well as emerging strategies for optimizing energy and redox balance in metabolic pathways. Finally, it highlights the emerging frontier of developing chemolithoautotrophic bacteria as microbial cell factories, capable of coupling carbon capture with sustainable biomanufacturing, thereby positioning these organisms at the forefront of next-generation climate and bioengineering solutions.