Reagent Engineering for Group Transfer Biocatalysis

iocatalysis has become a major driver in the innovation of preparative chemistry. Enzyme discovery, engineering and computational design have matured to reliable strategies in the development of biocatalytic processes. By comparison, substrate engineering has received much less attention. In this Minireview, we highlight the idea that the design of synthetic reagents may be an equally fruitful and complementary approach to develop novel enzyme-catalysed group transfer chemistry. This Minireview discusses key examples from the literature that illustrate how synthetic substrates can be devised to improve the efficiency, scalability and sustainability, as well as the scope of such reactions. We also provide an opinion as to how this concept might be further developed in the future, aspiring to replicate the evolutionary success story of natural group transfer reagents, such as adenosine triphosphate (ATP) and S-adenosyl methionine (SAM). Biocatalytic group transfer reactions can efficiently generate highly complex molecules under mild and environmentally friendly conditions. This Minireview highlights inspiring examples of the development of non-natural donor reagents to power such enzymatic transformations, while discussing the design aspects behind the choice of reagent.image

Automated summary

Enzyme catalysis is a major driver in preparative chemistry innovation, with relatively less attention given to substrate engineering. This Minireview highlights the idea that the design of synthetic reagents can be an equally fruitful approach in developing novel enzyme-catalyzed group transfer chemistry. It discusses key examples from the literature and provides an opinion on future development, aiming to replicate the success of natural group transfer reagents.