Enzyme-membrane-reactors: recent trends and applications for the production of fine chemicals and pharmaceutical building-blocks

Biocatalysis has gained attention in recent decades as a green and efficient method for producing high-value chemicals. Enzymes, notably due to their high selectivity, offer significant advantages for organic synthesis. However, industrial implementation remains limited due to challenges such as free enzyme instability, enzyme inhibition, and difficulties in catalyst recovery and reuse. The coupling of biocatalysis with membrane technology in enzyme-membrane-reactors (EMR) holds significant potential for process intensification, as it paves the way to continuous flow synthesis concatenated with product purification, and biocatalyst recovery. By allowing flow hybrid processes (i.e. simultaneous biocatalytic reactions and membrane operations in one-pot), EMR have the potential to increase reaction yields and kinetics, and reduce downstream processing requirements. This review explores recent trends and advancements in EMR for the production of pharmaceutical building blocks and fine chemicals. We examine the combination of enzymes with both polymeric and ceramic membranes, highlighting their respective benefits and limitations. We cover both EMR processes where free enzymes are used separately from membrane devices, and EMR processes employing membrane-immobilized enzymatic reactors. As enzyme immobilization in/on solid supports has emerged as an effective approach for enhancing enzyme stability and reusability, we argue that the development of such membrane-immobilized enzyme reactors is of prime importance for the pharmaceutical industry. These insights aim to provide a comprehensive overview of the role and recent applications of EMRs in advancing biocatalytic processes within the fine chemistry and pharmaceutical industry.