Additive Engineering of Water and “Water Mimic” in Lipase‐Catalyzed Aldol Reaction

Abstract The additive approach is widely used to enhance enzymatic activity in nonaqueous media. In this study, both formamide, known as “water mimics”, and water, significantly enhanced the promiscuous aldol reaction activity of lipase from porcine pancreas. However, only water changed the stereoselectivity of the tested aldol reaction. Experimental and computational results revealed the different roles played by water and formamide. Compared with water, formamide exhibited different effects and acted as a cocatalyst to activate substrates rather than a “water mimic” to “loosen up” enzymes in anhydrous solvents.