Enzyme activity in nonaqueous media (e.g. conventional organic solvents) is typically lower than in water by several orders of magnitude. There is a rising interest of developing new nonaqueous solvent systems that are more “water-like” and more biocompatible. Therefore, we need to learn from the current state of nonaqueous biocatalysis to overcome its bottleneck and provide guidance for new solvent design. This review firstly focuses on the discussion of how organic solvent properties (such as polarity and hydrophobicity) influence the enzyme activity and stability, and how these properties impact the enzyme’s conformation and dynamics. While hydrophobic organic solvents usually lead to the maintenance of enzyme activity, solvents carrying functional groups like hydroxys and ethers (including crown ethers and cyclodextrins) can lead to enzyme activation. Ionic liquids (ILs) are designable solvents that can conveniently incorporate these functional groups. Therefore, we systematically survey these ether- and/or hydroxy-functionalized ILs, and find most of them are highly compatible with enzymes leading to high activity and stability. In particular, ILs carrying both ether and tert-alcohol groups are among the most enzyme-activating solvents. Future direction is to learn from enzyme behaviors in both water and nonaqueous media to design biocompatible “water-like” solvents.

非水介质（例如常规有机溶剂）中的酶活性通常比水中低几个数量级。开发新的非水溶剂系统的兴趣日益浓厚，该系统更像“水”，并且具有更高的生物相容性。因此，我们需要学习非水生物催化的现状，以克服其瓶颈，并为新的溶剂设计提供指导。本文首先重点讨论有机溶剂的性质（如极性和疏水性）如何影响酶的活性和稳定性，以及这些性质如何影响酶的构象和动力学。疏水性有机溶剂通常会导致酶活性的维持，带有官能团（例如羟基和醚）（包括冠醚和环糊精）的溶剂会导致酶活化。离子液体（ILs）是可设计的溶剂，可以方便地合并这些官能团。因此，我们系统地调查了这些被醚和/或羟基官能化的IL，发现它们中的大多数与酶高度相容，从而导致了高活性和稳定性。特别是，携带醚和叔醇基团是最能激活酶的溶剂。未来的方向是学习在水和非水介质中的酶行为，以设计生物相容的“水样”溶剂。