Expanding the Synthetic Toolbox: Discovery of a Robust Aldehyde Dehydrogenase for Integrated Chemocatalysis and Enzyme Catalysis

Abstract Chemobiocatalysis has recently emerged as a promising tool in organic synthesis; nonetheless, chemobiocatalytic transformations remain challenging due to the incompatibility between the two types of catalysts. Many enzymes, especially aldehyde dehydrogenases (ALDHs), are readily inactivated under the chemocatalytic conditions. Herein, we present a robust NADP + ‐dependent p ‐hydroxybenzaldehyde dehydrogenase from Pseudomonas aeruginosa ( Pa HBDH) for integrated chemocatalysis and enzyme catalysis. Apart from good activities toward a number of aromatic aldehydes, Pa HBDH showed excellent thermal and storage stability in the absence of any stabilizer, but was also highly tolerant toward various organic solvents. The usefulness of Pa HBDH in integrated catalysis was demonstrated by the synthesis of a group of aromatic carboxylic acids in good yields by combining with photo‐/electrochemical NADP + regeneration. The photoenzymatic approach was further extended by integrating with a chemo(bio)catalytic cascade in one pot to allow for the conversion of furfural into value‐added C4 chemicals. The finding of this work may expand the synthetic toolbox for integrated catalysis.