The fourth wave of biocatalysis is approaching.

Biocatalysis has undergone a tremendous development in the past few years. A plethora of methods enable the rather rapid tailored-design of an enzyme for a targeted reaction such as asymmetric synthesis of a chiral building block by the combination of information from sequence and structure databases with modern molecular biology methods and high-throughput screening tools. Moreover, novel non-natural reactions could be implemented into protein scaffolds and new enzyme classes are emerging, both broadening the repertoire of reactions now available for organic synthesis. Furthermore, impressive examples of metabolic engineering-the combination of several newly introduced reaction steps in a microbial host-have been developed, paving the way for large-scale processes for both pharmaceuticals and bulk chemicals. This contribution highlights recent developments in this area and points out future challenges.This article is part of a discussion meeting issue 'Providing sustainable catalytic solutions for a rapidly changing world'.