Recent Advancements in Microbial Carbon Dioxide Fixation: Metabolic Engineering Strategies

Abstract

Global warming driven by rising CO2 emissions has spurred intense interest in biological carbon fixation as a sustainable alternative to physicochemical approaches. This review explores natural, engineering, and synthetic CO2 fixation strategies in both microbial and cell-free systems. We first outline canonical natural pathways, then highlight recent metabolic engineering approaches that enhance flux through native enzymes, optimize cofactor balances, and leverage CRISPR- and evolution-based tools to improve growth on CO2 or mixed C1 substrates. Next, we describe emerging synthetic routes, as well as electrochemical microbial hybrid systems that couple renewable electricity with biocatalysis. We then discuss downstream engineering tactics metabolic flux redirection, energy supply augmentation, regulatory gene editing, and enzyme design via directed evolution to overcome kinetic and thermodynamic barriers. High density cultivation, omics guided optimization, and non traditional hosts (acetogens, sulfate reducers, methanotrophs, methylotrophs, and yeasts) are surveyed for their industrial potential. Finally, we evaluate integration with waste gas streams, direct air capture platforms and biomass conversion, consider techno economic and scale up challenges, and identify opportunities for artificial intelligence driven pathway design. By uniting advances across biology, chemistry, and engineering, this review charts a roadmap toward efficient and scalable CO2-to-chemical bioproduction. Future progress in microbial CO2 fixation is expected to rely on the development of more efficient CO2-fixing enzymes and metabolic pathways, together with the incorporation of electro-biotechnology and optimized bioprocesses to enhance scalability and carbon conversion efficiency.