De novo design and evolution of an artificial metathase for cytoplasmic olefin metathesis.

ABSTRACT: Artificial metalloenzymes present a promising avenue for abiotic catalysis within living systems. However, their in vivo application is currently limited by critical challenges, particularly in selecting suitable protein scaffolds capable of binding abiotic cofactors and maintaining catalytic activity in complex media. Here we address these limitations by introducing an artificial metathase-an artificial metalloenzyme designed for ring-closing metathesis-for whole-cell biocatalysis. Our approach integrates a tailored metal cofactor into a hyper-stable, de novo-designed protein. By combining computational design with genetic optimization, a binding affinity (K _D ≤ 0.2 μM) between the protein scaffold and cofactor is achieved through supramolecular anchoring. Directed evolu

SUBMITTER: Zou Z 

PROVIDER: S-EPMC12638248 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature