Artificial Diels-Alderases at the service of green chemistry

To cope with the consequences of the anthropogenic cause of climate change, the chemical industry is forced to develop processes that are more respectful of the environment. Synthetic biology, using cellular factories such as micro-organisms, is part of this approach. Indeed, synthetic biology, which combines the regenerative power of micro-organisms with the synthetic potential of their metabolic pathways, is the application of the principles of sustainable development to the world of chemistry. Although new metabolic pathways are regularly discovered, the industrial use of life chemistry is still limited to a few major reactions. In particular, C-C bond-forming reactions, for which synthetic chemistry offers a wide range of variants, are underdeveloped in biocatalysis. Given this situation, one of the challenges of 21st-century chemistry is to enrich the field of biocatalysis by making biocompatible reactions that are currently not (or not very) biocompatible.

Artificial enzymes, derived from enzymes whose activity has been modified and/or redirected, or from enzymes created de novo, are the tools of choice for this new era in chemistry. The development of artificial enzymes for the benefit of fine chemistry goes hand in hand with spectacular progress in various fields of biocatalysis, such as the immobilization of enzymes on surfaces to lead to supported biocatalysts, directed evolution techniques, metabolic pathway engineering, in cellulo/in vivo catalysis and so on. In recent years, a growing number of artificial enzymes have been designed, including some that catalyze a Diels-Alder (DA) reaction. These have received particular attention because, until the end of the 20th century, DA reactions were considered to belong solely to the field of chemistry, and their introduction into biocatalysis represented a major challenge.

After a general introduction to biocatalysis and recent developments in its use on an industrial scale, the Diels-Alder reaction is presented, along with its many applications in synthesis. The central part of the article then turns to the discovery of enzymes capable of catalyzing the Diels-Alder reaction in living systems, and then focuses on the development of artificial metalloenzymes capable of catalyzing this reaction. This is followed by a discussion of the advantages and disadvantages of the various systems, concluding with a look at the prospects they offer.