Rising demands for efficient, selective, and versatile synthetic methods call for new enzymatic functions that may not be available in the biological realm. The challenges are daunting, requiring enzymes to take on new functions and requiring the newly developed biocatalysts to exhibit activity and selectivity comparable to or better than current chemocatalytic methods or fill gaps in synthetic chemistry. In this perspective, we summarize the current status of non-natural biocatalysis and describe how protein engineering, particularly directed evolution integrated with chemical rationalization, enables innovations that expand the chemical space accessible to enzymes. The creation of abiological enzymatic functions represents a growing area of research that requires knowledge from different fields, including protein engineering, enzymology, and synthetic chemistry.

对高效、选择性和多功能合成方法日益增长的需求需要生物领域可能无法提供的新酶功能。挑战是艰巨的，需要酶具有新的功能，需要新开发的生物催化剂表现出与当前化学催化方法相当或更好的活性和选择性，或填补合成化学领域的空白。从这个角度来看，我们总结了非天然生物催化的现状，并描述了蛋白质工程，特别是与化学合理化相结合的定向进化，如何实现扩大酶可利用的化学空间的创新。非生物酶功能的创造代表了一个不断增长的研究领域，需要不同领域的知识，包括蛋白质工程、酶学和合成化学。