Congratulations to Nansook, who published a paper in Biochemistry together with collaborators from the Tokuriki lab: “Conformational tinkering drives evolution of a promiscuous activity through indirect mutational effects”. [link]
In this work, we used laboratory evolution to effect a thousand-fold increase in phosphotriesterase activity in a lactonase enzyme. Mutations acquired during evolution altered the position of an active site residue that previously had no functional role, improving the alignment of the substrate in the active site and thereby increasing phosphotriesterase activity. This work gives a detailed picture of how “conformational tinkering” by remote mutations can allow large increases in enzyme activity.