Cooperativity and flexibility in enzyme evolution

Enzymes are flexible catalysts, and there has been substantial discussion about the extent to which this flexibility contributes to their catalytic efficiency. What has been significantly less discussed is the extent to which this flexibility contributes to their evolvability. Despite this, recent years have seen an increasing number of both experimental and computational studies that demonstrate that cooperativity and flexibility play significant roles in enzyme innovation. This review covers key developments in the field that emphasize the importance of enzyme dynamics not just to the evolution of new enzyme function(s), but also as a property that can be harnessed in the design of new artificial enzymes.The European Research Council has provided financial support under the European Community’s Seventh Framework Program (FP7/2007-2013)/ERC Grant Agreement No. 306474. This work was also funded by the Feder Funds, Grants from the Spanish Ministry of Economy and Competitiveness (BIO2015-66426-R and CSD2009-00088) and the Human Frontier Science Program (RGP0041/2017). A.P. is a Wenner-Gren Foundations Postdoctoral Fellow and S. C. L. K. is a Wallenberg Academy Fellow