Nitrite Reductases in Biomedicine: From Natural Enzymes to Artificial Mimics

Nitrite reductases (NiRs) are natural enzymes that facilitate the reduction of nitrite. They are essential for the microbial nitrogen cycle and play a vital role in regulating numerous physiological and pathological processes associated with nitric oxide (NO) in living organisms. By the merits of protein engineering, a variety of artificial NiR mimics have been developed. These include traditional artificial proteins, metal-azacycle complexes, and nanozymes such as metal, metal oxide/sulfide nanoparticles, metal-organic frameworks, bioinorganic nanohybrids, and advanced single-atom nanozymes. This development marks an important milestone in broadening the application of enzyme-like catalytic nitrite reduction across various fields, such as biomedicine, biosensing, food science, and environmental science. In this review, we first outline the different types of NiRs, along with their active center structures and catalytic mechanisms, drawing from recent research and discoveries. We then classify the reported NiR mimic materials, discussing their active center structures and enzyme-like catalytic mechanisms. Additionally, we explore the potential future applications and challenges facing NiR mimics in the field of biomedicine.