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.

酶级联是一种强大的技术，可以开发环境友好且具有成本效益的合成工艺来制造药物，因为它们在连续反应中结合不同的生物转化来合成产品。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通过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，我们概述了用于体内（全细胞）或体外（纯化酶）的多种酶级联反应，专门针对药物相关分子，从简单的构建块到复杂的药物。我们还通过一系列报道的例子讨论了多步酶级联的优点和要求以及它们与化学催化剂的结合。最后，我们研究了酶级联的效率，以及如何通过酶工程、流动反应器中的工艺强化和/或酶固定化来进一步改进它们，以满足所有工业要求。