“…Single-atom nanozymes featuring well-defined M–N x (M = Fe, Co, Pt, Mn, and Cu) sites are new enzyme-mimicking candidates, which have been widely applied in tumor therapy, disinfection, and other fields. − The maximum atom utilization and similarity of M–N x sites to those of natural metalloenzymes endow SAzymes with a higher catalytic activity than conventional nanozymes. − However, they have a limited catalytic activity compared to natural enzymes, which restricts their performance and further application. Recently, the manipulation of the surrounding atomic configuration of SAzymes has been widely adopted to improve their catalytic activity. − For example, the catalytic performance of SAzymes can be regulated by tuning the coordination numbers of the single metal sites. − Likewise, replacing coordinated nitrogen with other elements to form Fe/CoN 3 P or FeN 3 S could enhance enzyme-like activity via near–range interactions. − Heteroatom doping (for example, with phosphorus and boron) of the carbon matrix can also enhance the peroxidase-like (POD-like) activity of the Fe center through long–range interactions. , Despite the significant advances made, the active sites in SAzymes are still generally two-dimensional (2D) and isolated catalytic units.…”