Natural Evolution Provides Strong Hints about Laboratory Evolution of Designer Enzymes.

ABSTRACT: Laboratory evolution combined with computational enzyme design provides the opportunity to generate novel biocatalysts. Nevertheless, it has been challenging to understand how laboratory evolution optimizes designer enzymes by introducing seemingly random mutations. A typical enzyme optimized with laboratory evolution is the abiological Kemp eliminase, initially designed by grafting active site residues into a natural protein scaffold. Here, we relate the catalytic power of laboratory-evolved Kemp eliminases to the statistical energy ([Formula: see text]) inferred from their natural homologous sequences using the maximum entropy model. The [Formula: see text] of designs generated by directed evolution is correlated with enhanced activity and reduced stability, thus displaying a stability-a

SUBMITTER: Xie WJ 

PROVIDER: S-EPMC9351539 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature