Directed evolution of a TNA polymerase identifies independent paths to fidelity and catalysis.

ABSTRACT: Directed evolution facilitates functional adaptations through stepwise changes in sequence that alter protein structure. While most campaigns yield solutions that maintain the framework of a rigid protein architecture, a few have produced enzymes with more notable structural differences. One example is a polymerase that was evolved to synthesize threose nucleic acid (TNA) with near-natural activity. Understanding how this enzyme arose provides a model for studying pathways that guide enzymes toward more productive regions of the fitness landscape. Here, we trace the evolutionary trajectory of an unnatural polymerase by solving crystal structures of key intermediates along the pathway and evaluating their biochemical activity. Contrary to the view that fidelity is a product of increased cat

SUBMITTER: Hajjar M 

PROVIDER: S-EPMC12830623 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature