“Cryptic genetic variation shapes the adaptive evolutionary potential of enzymes” – new paper

New eLIFE paper available online now! https://elifesciences.org/articles/40789

In this work, a collaboration with members of the Tokuriki (UBC) and Kamerlin (Upsalla University) groups, we performed directed evolution of four orthogous metallo-beta-lactamases towards a new function and found that different starting genotypes led to distinct evolutionary outcomes. We used a range of techniques, including directed evolution, enzyme kinetics, stability assays, X-ray crystallography and molecular dynamics to explore the differences in the structural and functional changes that occurred along each of these evolutionary pathways.

This work highlights the importance of understanding the molecular details that connect genetic variation to protein function to improve the prediction of protein evolution. The results from this work suggest that it may be effective to explore diverse initial genotypes when attempting to engineer or evolve new protein functions.

Congratulations to Nansook and all others that worked on this paper!