Biocatalysis takes to flow


School of Chemistry, University of Nottingham,
Nottingham, United Kingdom


The use of enzymes in industrial processes is increasing and with it also the need to develop highly efficient systems which combine the advantages of biocatalysis with high productivity. Several processes have recently appeared in the literature which have brought the use of enzymes to another level: immobilised whole cells expressing the biocatalyst, as well as pure enzymes, have been successfully applied in the continuous productions of valuable products, exploiting the flexibility of flow bioreactors. Continuous flow biocatalysis is the ultimate evolution of continuous processing and is bringing enzymes into a whole new dimension: while cofactor-free system are readily being implemented, cofactor-dependent enzymes are still a challenge.

Enzymatic processes have been known and utilized for over a century in different industrial settings, for food manufacturing, detergents, and more recently in the production of fine chemicals, pharmaceuticals, agrochemical, and cosmetics (1).

Nowadays, with exceptional progresses in enzyme engineering, enzymes can be precisely designed to fit a bespoke process. Directed evolution, rational design, and effective screening methods have been reported essentially for all enzymatic classes. Manipulation of enzymatic physico-chemical properties has led to the engineering of proteinases which retain activity over 100 °C (2), enzymes capable to withstand the presence of highly organic solvents such as dimethyl-formamide (3), and a vast array of enzymes with non-natural activity against synthetic substrates (4).

Despite these advances, it is remarkable that while over 4000 enzymes have been characterized, only 200 of microbial origin are used commercially, and just about 20 enzymes are produced on a truly industrial scale (5). The largest cohort is represented by the application of natural hydrolytic enzymes (proteases, lipases, amylases, and cellulases) for textile, det ...