[Enzymatic intermolecular Stetter reaction catalyzed by benzaldehyde lyase].

Biocatalysis, as a fundamental enabling technology of biomanufacturing, is indispensable for promoting the green and efficient transformation of industrial processes. The catalytic disorder of enzymes provides key support for the development of new chemical conversions that do not exist in nature. Therefore, we urgently need to expand the diverse new functions of enzymes. In this study, we report a case of an unnatural intermolecular Stetter reaction catalyzed by natural benzaldehyde lyase (pfBAL). Benzaldehyde lyase activates benzaldehyde to undergo an addition reaction with the imine substrate formed in situ, and thus an unnatural amino ketone is obtained. Through systematic screening and optimization of reaction conditions, the yield of the target product was enhanced, and a certain range of substrate applicability was demonstrated. This study demonstrates that the benzaldehyde lyase pfBAL exhibits catalytic activity in mediating the Stetter reaction between unnatural molecules, laying a theoretical foundation for the future expansion of diverse catalytic functions of this enzyme.