In-depth Sequence-Function Characterization Reveals Multiple Pathways to Enhance Enzymatic Activity.

ABSTRACT: Deep mutational scanning (DMS) has recently emerged as a powerful method to study protein sequence-function relationships but it has not been well-explored as a guide to enzyme engineering and identifying pathways by which their catalytic cycle may be improved. We report such a demonstration in this work using a Phenylalanine ammonia-lyase (PAL), which deaminates L-phenylalanine to trans-cinnamic acid and has widespread application in chemo-enzymatic synthesis, agriculture, and medicine. In particular, the PAL from Anabaena variabilis (AvPAL*) has garnered significant attention as the active ingredient in Pegvaliase^®, the only FDA-approved drug treating classical Phenylketonuria (PKU). Although an extensive body of literature exists on the structure, substrate-spec

SUBMITTER: Trivedi VD 

PROVIDER: S-EPMC10270700 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature