Biocatalytic amide bond formation

Amide bonds occur in over half of target compounds in medicinal chemistry patents, making amide bond formation the most commonly performed reaction in the pharmaceutical industry. The growing demand for green and sustainable catalytic methods for amide bond synthesis has driven the interest in biocatalytic methods. We have compiled the literature on this topic in a publicly available database (RetroBioCat) and use this database to discuss the most commonly used strategies. These include the use of low water systems for driving equilibria and kinetics in hydrolase-catalysed reactions towards amide bond formation. Alternatively, in aqueous medium, ATP-dependent enzymes have been shown to be particularly promising and can be coupled to ATP recycling systems.