MARTINA L. CONTENTE
Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy

Abstract

The number of biocatalyzed reactions in the industrial context is growing rapidly together with our understanding on how we can maximize the enzyme productivity increasing catalyst efficiency and stability. Although biocatalysis is nowadays identified as a greener way to operate in chemistry, its incorporation in flow reactors has lately come up as a powerful tool to enhance process productivity, sustainability and selectivity. This opinion article aims at describing the recent advances of this technology and future developments allowing for efficient, smart and environmentally-friendly strategies for process optimization and large scale production.

Introduction
The fast evolution of enzyme engineering during the last decade has dramatically impacted the number of industrial processes that involve one or more biocatalytic steps for the preparation of fine chemicals including pharmaceuticals, cosmetics, agrochemicals and bioactive compounds (1). Among the most impressive examples in the pharmaceutical sector, the enzymatic total synthesis of Islatravir, a nucleoside reverse transcriptase translocation inhibitor (NRTTI) for HIV infection, has been achieved by Merck in 2019 (2). Nine enzymes, most of which had to be carefully engineered, were required for the accomplishment of such a synthesis, with four of those biocatalysts serving exclusively as ancillary systems for cofactor recycling or equilibrium shifting. Another inspiring example regards the heavily engineered transaminase ATA 117 employed as a key catalyst to replace a rhodium-mediated asymmetric enamine hydrogenation step for the preparation of the blockbuster drug Sitagliptin (3). Additionally, starting from tropical berries a particular protein has been prepared by Amai Proteins company. Due to its sweetening power (3000 times sweeter than ...