Unlocking the Potential of Flow Biocatalysis with Enzyme Immobilization.

Flow biocatalysis combines the superior selectivity and sustainability of enzymes with the flexibility, automation potential, and enhanced productivity of continuous manufacturing. However, to apply a biocatalytic step in flow, some intrinsic limitations of biocatalysts must be addressed, especially their stability and reusability. Thus, enzyme immobilization is a key enabling technology and remains a critical step and one of the main bottlenecks. Immobilizing enzymes on solid supports improves their stability, reusability, and compatibility with flow conditions, but it is limited by the trial-and-error approach at the development stages. In this short perspective, we discuss recent innovations in enzyme immobilization, including in silico design, the combination with 3D printing and high-throughput screening, and present selected examples of applications in flow of immobilized enzymes, with a particular focus on process flexibility and their combination into chemoenzymatic cascades.