An Artificial Metalloenzyme for Atroposelective Metathesis**

AbstractAtropisomers – separable conformers that arise from restricted single‐bond rotation – are frequently encountered in medicinal chemistry. However, preparing such compounds with the desired configuration can be challenging. Herein, we present a biocatalytic strategy for achieving atroposelective synthesis relying on artificial metalloenzymes (ArMs). Based on the biotin‐streptavidin technology, we constructed ruthenium‐bearing ArMs capable of producing atropisomeric binaphthalene compounds through ring‐closing metathesis in aqueous media. Further, we show that atroposelectivity can be fine‐tuned by engineering two close‐lying amino acid residues within the streptavidin host protein. The resulting ArMs promote product formation with enantiomeric ratios of up to 81 : 19, while small‐molecule catalysts for atroposelective metathesis under aqueous reaction conditions are yet unknown. This study represents the first demonstration that stereoselective metathesis can be achieved by an artificial metalloenzyme.