Programmable enzyme catalysis based on multiscale confinements

Enzymes are powerful catalysts in nature, enabling the sustainable and efficient synthesis of complex biomolecules. The remarkable efficiency of enzymes arises from the intricately organized and spatially confined intracellular environment. Inspired by nature, researchers are increasingly applying these principles to design extracellular enzyme catalysts with enhanced performance. Multiscale confinement serves as a unifying strategy for programmable biocatalysis. This approach includes (1) confining metal atoms or catalytic residues within enzyme active sites to create artificial enzymes, (2) immobilizing enzymes on surfaces or within nanocarriers to enhance stability and efficiency and (3) restricting the diffusion of reaction intermediates to mimic substrate channelling in multienzyme complexes. This Review examines how multiscale confinement can be harnessed for superior catalyst design in organic synthesis. Recent advancements are highlighted, and current challenges, as well as future directions for this rapidly evolving field, are discussed. (Figure presented.)