Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.
Nat Chem. 2022 May;14(5):489-499. doi: 10.1038/s41557-022-00931-2. Epub 2022 May 5.
Enzyme cascades are a powerful technology to develop environmentally friendly and cost-effective synthetic processes to manufacture drugs, as they couple different biotransformations in sequential reactions to synthesize the product. These biocatalytic tools can address two key parameters for the pharmaceutical industry: an improved selectivity of synthetic reactions and a reduction of potential hazards by using biocompatible catalysts, which can be produced from sustainable sources, which are biodegradable and, generally, non-toxic. Here we outline a broad variety of enzyme cascades used either in vivo (whole cells) or in vitro (purified enzymes) to specifically target pharmaceutically relevant molecules, from simple building blocks to complex drugs. We also discuss the advantages and requirements of multistep enzyme cascades and their combination with chemical catalysts through a series of reported examples. Finally, we examine the efficiency of enzyme cascades and how they can be further improved by enzyme engineering, process intensification in flow reactors and/or enzyme immobilization to meet all the industrial requirements.
酶级联反应是一种强大的技术，可以开发环保且具有成本效益的合成工艺来制造药物，因为它们可以将不同的生物转化在连续反应中偶联起来，以合成产物。这些生物催化工具可以解决制药行业的两个关键参数：提高合成反应的选择性和使用生物相容性催化剂减少潜在危害，这些催化剂可以从可持续来源生产，可生物降解，通常无毒。在这里，我们概述了广泛的酶级联反应，无论是在体内（整个细胞）还是体外（纯化酶），都可以专门针对具有药用价值的分子，从简单的构建块到复杂的药物。我们还讨论了多步酶级联反应的优点和要求，以及通过一系列报道的实例将其与化学催化剂结合的情况。最后，我们研究了酶级联反应的效率，以及如何通过酶工程、在流动反应器中的过程强化和/或酶固定化进一步提高其效率，以满足所有工业要求。
