Biocatalytic Approaches to Amide Synthesis

Although amide bonds are among the most ubiquitous functional groups found within organic molecules, traditional chemical methods of amide synthesis present a number of shortcomings. Enzymes, which typically exhibit high selectivity and function under benign conditions in aqueous media, can address some of the issues encountered with chemical synthesis of amides. Early approaches to biocatalytic amide synthesis employed hydrolase enzymes such as lipases, esterases, acylases or proteases operating in the reverse synthetic direction often requiring organic solvents. However, in recent years powerful ATP-dependent ligases have been discovered, engineered and deployed for amide assembly. In this review we will discuss the advantages and disadvantages of the different biocatalysts available for amide synthesis, from hydrolases and nitrile hydratases, through to amide bond synthetase (ABS), ATP-grasp and other specialized ligase enzymes.