Improving Enzyme Fitness with Machine Learning

The combinatorial composition of proteins has triggered the application of machine learning in enzyme engineering. By predicting how protein sequence encodes function, researchers aim to leverage machine learning models to select a reduced number of optimized sequences for laboratory measurement with the aim to lower costs and shorten timelines of enzyme engineering campaigns. In this review, we highlight successful algorithm-aided protein engineering examples, including work carried out within NCCR Catalysis. In this context, we will discuss the underlying computational methods developed to improve enzyme properties such as enantioselectivity, regioselectivity, activity, and stability. Considering the rapid maturing of computational techniques, we expect that their continued application in enzyme engineering campaigns will be key to deliver additional powerful biocatalysts for sustainable chemical synthesis.