Enzymatic CO₂ reduction catalyzed by natural and artificial Metalloenzymes

The continuously increasing level of atmospheric CO₂ in the atmosphere has led to global warming. Converting CO₂ into other carbon compounds could mitigate its atmospheric levels and produce valuable products, as CO₂ also serves as a plentiful and inexpensive carbon feedstock. However, the inert nature of CO₂ poses a major challenge for its reduction. To meet the challenge, nature has evolved metalloenzymes using transition metal ions like Fe, Ni, Mo, and W, as well as electron-transfer partners for their functions. Mimicking these enzymes, artificial metalloenzymes (ArMs) have been designed using alternative protein scaffolds and various metallocofactors like Ni, Co, Re, Rh, and FeS clusters. Both the catalytic efficiency and the scope of CO₂-reduction product of these ArMs have been improved over the past decade. This review first focuses on the natural metalloenzymes that directly reduce CO₂ by discussing their structures and active sites, as well as the proposed reaction mechanisms. It then introduces the common strategies for electrochemical, photochemical, or photoelectrochemical utilization of these native enzymes for CO₂ reduction and highlights the most recent advancements from the past five years. We also summarize principles of protein design for bio-inspired ArMs, comparing them with native enzymatic systems and outlining challenges and opportunities in enzymatic CO₂ reduction.