The “greenhouse effect” gradually intensifies as many greenhouse gases are released. The United Nations Secretary-General Antonio Guterres said, “The era of global warming has ended; the era of global boiling has arrived.” Solving the problem of the “greenhouse effect” is urgently required. The greenhouse gases include CO2, methane, N2O, and other greenhouse gases. The proportion of CO2 in greenhouse gases has increased to 76.7% (v/v), making it the primary cause of climate change (Kajla et al., 2022). Notably, the current CO2 level in the atmosphere is almost twice that of the preindustrial period. Fig. 1 shows the change in global CO2 concentration, annual growth rates, and average growth every five years over the last 40 years. This result shows that the CO2 levels are increasing steadily and that the increase is accelerating. The accumulation of CO2 has long-term adverse consequences, including glaciers decrease, permafrost melt, ocean acidification, snowpack decrease, etc. Therefore, controlling and decreasing CO2 leaves has become a primary concern.

One strategy for achieving this aim is to use biological systems to convert CO2 into multi‑carbon compounds. This approach reduces CO2 emissions while providing a free carbon source for the biosynthesis of multi‑carbon products, resulting in a win-win situation. The biological conversion of CO2 has garnered much interest due to its gentle process conditions, eco-friendly approach, and product selectivity. The development of biological CO2 fixation research has led to the discovery of natural CO2 fixation pathways for constructing artificial CO2 fixation pathways. Until 2021, six natural CO2-fixation routes have been reported. These pathways can be separated into aerobic and anaerobic CO2-fixation pathways, depending on the presence of specific oxygen-sensitive enzymes. Aerobic pathways include the Calvin cycle (the CBB cycle), the 3-hydroxypropionate (3HP) cycle, and the 3-hydroxypropionate-4-hydroxybutyrate (3HP/4HB) cycle. Anaerobic pathways comprise the reductive tricarboxylic acid (rTCA) cycle, the Wood-Ljungdahl (WL) pathway, and the dicarboxylate/4-hydroxybutyrate (DC/4HB) cycle. However, natural CO2-fixation pathways are energy intensive or thermodynamically unfavorable (Zhao et al., 2021). Therefore, artificial CO2-fixation pathways with improved efficiency were designed. Artificial CO2-fixation pathways can be divided into two categories according to the properties of critical carbon-fixing enzymes: carboxylase-mediated synthetic CO2-fixation pathways and reductase-mediated synthetic CO2-fixation pathways(Jiang et al., 2020). The carboxylase-mediated synthetic CO2-fixation pathways include malonyl-CoA-oxaloacetate-glyoxylate pathway (MOG), malonyl-CoA-glycerate pathway (MCG), crotonyl-CoA/ethylmalonyl-CoA/hydroxybutyrate-CoA cycle (CETCH), and POAP cycle. Reductase-mediated synthetic CO2-fixation pathways include the reductive glycine pathway (rGly), formolase pathway, synthetic acetyl-CoA pathway (SACA), and artificial starch anabolic pathway (ASAP).

In CO2 bioconversion process, CO2 first enters carbon fixation pathways at different levels. After a series of metabolic reactions, CO2 can then be converted into reducing intermediate metabolites, such as pyruvate or acyl-CoA. These products can be used as critical metabolic intermediates for cell growth or as building blocks to produce long-chain carbon compounds. CO2 molecules have the highest oxidation state (+4 valence state), whereas typical multi‑carbon chemicals (hydrocarbons, aldehydes, acids, or alcohols) have lower valence states. Consequently, the Gibbs free energy (ΔG) changes of CO2 reductive processes are generally positive and this makes it necessary to input different forms of energy for carbon fixation. Up to now, various designs to improve CO2 fixation efficiency of autotrophic and heterotrophic microorganisms have been reported. This review discusses the latest progress in optimizing CO2 biological fixation. Initially, it examined the thermodynamic properties of carbon fixation reactions and proposed optimization directions to enhance their efficiency. Subsequently, the catalytic mechanisms and optimization techniques employed by core carbon fixation enzymes are summarized. Additionally, it focuses on optimization strategies for ATP, reducing power, energy supply modules, reactor design, and carbon enrichment systems. Recent advances in artificial carbon fixation pathways have also been described. Finally, the perspectives of CO2 biological fixation are discussed.