Directed Evolution of a Protein Catenane Reveals How Noncanonical Topology Modulates Sequence–Property Relationships
Single-domain protein catenanes, in which two mechanically interlocked polypeptide rings fold into a compact structure, provide a tractable system for probing how chemical topology reshapes protein fitness. Using single-domain catenated dihydrofolate reductase (cat-DHFR) as a model, we combined homologue expansion, d...