Recent progress in engineering alpha/beta hydrolase-fold family members

The members of the alpha/beta hydrolase-fold family represent a functionally versatile group of enzymes with many important applications in biocatalysis. Given the technical significance of alpha/beta hydrolases in processes ranging from the kinetic resolution of enantiomeric precursors for pharmaceutical compounds to bulk products such as laundry detergent, optimizing and tailoring enzymes for these applications presents an ongoing challenge to chemists, biochemists, and engineers alike. A review of the recent literature on alpha/beta hydrolase engineering suggests that the early successes of "random processes" such as directed evolution are now being slowly replaced by more hypothesis-driven, focused library approaches. These developments reflect a better understanding of the enzymes' structure-function relationship and improved computational resources, which allow for more sophisticated search and prediction algorithms, as well as, in a very practical sense, the realization that bigger is not always better.