Flow bioreactors as complementary tools for biocatalytic process intensification

Biocatalysis has widened its scope and relevance since new molecular tools, including improved expression systems for proteins, protein and metabolic engineering, and rational techniques for immobilization, have become available. However, applications are still sometimes hampered by low productivity and difficulties in scaling up. A practical and reasonable step to improve the performances of biocatalysts (including both enzymes and whole-cell systems) is to use them in flow reactors. This review describes the state of the art on the design and use of biocatalysis in flow reactors. The encouraging successes of this enabling technology are critically discussed, highlighting new opportunities, problems to be solved and technological advances. Biocatalyzed reactions with different classes of enzymes can be implemented with the integration of flow reactor technology, potentially leading to sustainable and highly productive continuous processes.The combination of biocatalysis and flow chemistry opens the door to extensive application in cascade reactions.Biocatalyzed flow reactions can occur either in monophasic flow or in segmented (slug) flow, where two or more immiscible phases are present.Limitation of substrate/product inhibition effects, in-line purification with easy recovery of the product, and no mechanical mixing are among the most distinctive advantages of flow-based biocatalysis.Automated machines and devices for in-line product recovery are now available at relatively low prices, making flow-based biocatalysis an easy-to-use technology.