Multienzyme Cascade Reactions: Compatibility, Cooperativity, and Control

Multienzyme cascades combine several biocatalytic reactions in a single synthetic operation without isolation of intermediates. Compared to traditional multistep sequences, they offer significant advantages in terms of time and resource efficiency, and they often enable overall transformations that would not be possible by performing the constituent steps independently of each other. In this review article, we highlight selected multienzyme cascades from the recent literature (mainly 2020–2025) and discuss their main benefits and challenges along three overarching themes: compatibility of the required chemical transformations and biocatalysts, cooperativity between enzymes that operate concurrently in the same vessel, and control over the final outcome of the complete reaction sequence. Cascade designs that account for these aspects have enabled the expedient synthesis of a broad range of relevant target compounds, including complex pharmaceutical drugs prepared on industrial scale.