Intramolecular Stereoselective Stetter Reaction Catalyzed by Benzaldehyde Lyase.

The reliable design and prediction of enzyme promiscuity to access transformations not observed in nature remains a long‐standing challenge. Herein, we present the first example of an intramolecular stereoselective Stetter reaction catalyzed by benzaldehyde lyase, guided by the rational structure screening of various ThDP‐dependent enzymes using molecular dynamics (MD) simulations. After optimization, high productivity (up to 99 %) and stereoselectivity (up to 99:1 e.r.) for this novel enzyme function was achieved. [ABSTRACT FROM AUTHOR]