Speeding up enzyme discovery and engineering with ultrahigh-throughput methods

Exploring the sequence space of enzyme catalysts is ultimately a numbers game. Ultrahigh-throughput screening methods for rapid analysis of millions of variants are therefore increasingly important for investigating sequence-function relationships, searching large metagenomic libraries for interesting activities, and accelerating enzyme evolution in the laboratory. Recent applications of such technologies are reviewed here, with a particular focus on the practical benefits of droplet-based microfluidics for the directed evolution of natural and artificial enzymes. Broader implementation of such rapid, cost-effective screening technologies is likely to redefine the way enzymes are studied and engineered for academic and industrial purposes.