Evolutionary Specialization of a Promiscuous Designer Enzyme.

ABSTRACT: The evolution of a promiscuous enzyme for its various activities often results in catalytically specialized variants. This is an important natural mechanism to ensure the proper functioning of natural metabolic networks. It also acts as both a curse and blessing for enzyme engineers, where enzymes that have undergone directed evolution may exhibit exquisite selectivity at the expense of a diminished overall catalytic repertoire. We previously performed two independent directed evolution campaigns on a promiscuous designer enzyme that leverages the unique properties of a noncanonical amino acid (ncAA) para-aminophenylalanine (pAF) as catalytic residue, resulting in two evolved variants which are both catalytically specialized. Here, we combine mutagenesis, crystallography, and comput

SUBMITTER: Leveson-Gower RB 

PROVIDER: S-EPMC11811923 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature