Approaches for regulating enzyme activities: Recent advances in experiment and computation

Major progress has been made in recent years in terms of strategies for regulating enzyme activities. Novel high-throughput enzyme kinetic assays and efficient computational methodologies enabled a deeper understanding of molecular mechanisms that dictate the activity of enzymes, which provide guidance to rational modulation of enzyme catalysis. Continued development of efficient screening, directed evolution technologies, and machine learning–driven protein engineering tools make it possible to tune enzyme activities without having to understand the detailed mechanism of catalysis regulation. By combining these two limiting approaches, the efficiency of enzyme regulation can be substantially improved as a mechanistic understanding can help reduce the size of design space before the ‘brute-force’ engineering approach takes over. We briefly discuss relevant advances in both experiment and computation and comment on future developments that can further enhance mechanistic understanding and engineering capability for broad applications.