Enantiocomplementary Intramolecular Crossed Aldehyde-Ketone Benzoin Cyclizations Catalyzed by Engineered Benzaldehyde Lyase

Developing unnatural functions and optimizing catalytic properties of enzymes are challenging tasks that require extensive engineering and screening of biocatalysts. In this study, we report the first example of enantiocomplementary intramolecular crossed aldehyde-ketone benzoin cyclizations catalyzed by benzaldehyde lyase. Benefiting from the utilization of structure prediction and molecular simulations, we efficiently designed and optimized enzyme mutants capable of achieving this novel catalytic function with high yields (up to 97%) and excellent enantioselectivity (up to 99:1 e.r).