Evolutionary insights into the stereoselectivity of imine reductases based on ancestral sequence reconstruction.

ABSTRACT: The stereoselectivity of enzymes plays a central role in asymmetric biocatalytic reactions, but there remains a dearth of evolution-driven biochemistry studies investigating the evolutionary trajectory of this vital property. Imine reductases (IREDs) are one such enzyme that possesses excellent stereoselectivity, and stereocomplementary members are pervasive in the family. However, the regulatory mechanism behind stereocomplementarity remains cryptic. Herein, we reconstruct a panel of active ancestral IREDs and trace the evolution of stereoselectivity from ancestors to extant IREDs. Combined with coevolution analysis, we reveal six historical mutations capable of recapitulating stereoselectivity evolution. An investigation of the mechanism with X-ray crystallography shows that they collect

SUBMITTER: Zhu XX 

PROVIDER: S-EPMC11605051 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature