Abstract
Biocatalysts represent an efficient, highly selective and greener alternative to metal catalysts in both industry and academia. In the last two decades, the interest in biocatalytic transformations has increased due to an urgent need for more sustainable industrial processes that comply with the principles of green chemistry. Thanks to the recent advances in biotechnologies, protein engineering and the Nobel prize awarded concept of direct enzymatic evolution, the synthetic enzymatic toolbox has expanded significantly. In particular, the implementation of biocatalysts in continuous flow systems has attracted much attention, especially from industry. The advantages of flow chemistry enable biosynthesis to overcome well-known limitations of “classic” enzymatic catalysis, such as time-consuming work-ups and enzyme inhibition, as well as difficult scale-up and process intensifications. Moreover, continuous flow biocatalysis provides access to practical, economical and more sustainable synthetic pathways, an important aspect for the future of pharmaceutical companies if they want to compete in the market while complying with European Medicines Agency (EMA), Food and Drug Administration (FDA) and green chemistry requirements. This review focuses on the most recent advances in the use of flow biocatalysis for the synthesis of active pharmaceutical ingredients (APIs), pharmaceuticals and natural products, and the advantages and limitations are discussed.
Highlights
The term “biocatalysis” refers to the use of enzymes, both as purified proteins or as whole cells, to catalyze the conversion of a substrate into a desired product, and it is currently a popular topic in synthetic research [1]
Besides the above-reported synthesis of terpenes having a direct role in active pharmaceutical ingredients (APIs) preparations, some interesting examples of flow biocatalysis applied to the synthesis of natural products were recently reported
A review of the most recent literature evidenced that the use of biocatalysts in continuous flow systems could represent an efficient, green and sustainable alternative for industrial processes in the synthesis of APIs and pharmaceutically-relevant synthons
Summary
The term “biocatalysis” refers to the use of enzymes, both as purified proteins or as whole cells, to catalyze the conversion of a substrate into a desired product, and it is currently a popular topic in synthetic research [1]. “natural” enzymes have been found to catalyze “non-natural” synthetic reactions and are capable of increasing their stability by direct evolution to better adapt themselves to “non-natural” reaction conditions [12,13,14,15] This higher selectivity leads to more straightforward synthetic pathways with no functionalization steps needed, resulting in reduced wastes [16,17]. This increased interest in flow biocatalysis arose from the possibility of merging the conveniences of enabling technologies and the advantages of enzymatic catalysis into versatile, greener and sustainable synthetic tools. Other aspects recently included in comprehensive reviews reported by De Santis et al [34] and Britton et al [36], as well as the catalysts special issue “Flow Biocatalysis” edited by Professor Paradisi [39], will be not discussed in the present article
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