Researchers at the University of Amsterdam have developed a new method for producing amides and thioesters using engineered alcohol dehydrogenase (ADH) enzymes.[1][2] Enzymes work by oxidizing an alcohol to an aldehyde, which then combines with an amine or thiol to form an intermediate hemiaminal or hemithioacetal.[2] The enzyme then performs a second oxidation step that leads to the formation of an amide or thioester.[2] This method achieves yields of up to 99% using only 0.1 mol% of the enzyme in relation to the alcohol substrate.[1][2] The production takes place without the need for expensive chemicals, activated intermediates or harsh reaction conditions – all you need is an enzyme, air and a water buffer.[1][2] Using protein engineering, researchers expanded the active site of the enzyme by mutating key residues, which made it possible to process even larger molecules of amines and thiols.[1][2] This application of ADH enzymes paves the way for the efficient and clean production of amides and thioesters, which are highly valued in the industrial synthesis of drugs and advanced materials.[1]