Flow Synthesis of Pharmaceutical Intermediate Catalyzed by Immobilized DERA: Comparison of Different Immobilization Techniques and Reactor Designs

The enzymatic synthesis of statin intermediates offers a sustainable alternative to traditional multistep chemical methods. This study investigates the continuous flow synthesis of statin precursors in a millireactor using 2-deoxy-D-ribose-5-phosphate aldolase (DERA) immobilized on mesoporous silica foam (MCF) and magnetic nanoparticles (MNPs). Two types of flow millireactors, a fixed bed millireactor for MCF and a fluidized bed millireactor for MNP, were designed. Key performance indicators including conversion, selectivity, yield, and productivity were analyzed and compared with the batch reactor results. The MNP-based fluidized bed millisystem demonstrated superior conversion (97.78%) and yield (95.85%) under optimized conditions, outperforming both batch and MCF-based millisystems. This work highlights the importance of optimizing immobilization techniques and reactor configurations to enhance enzyme stability and catalytic efficiency in continuous biocatalytic processes, particularly for pharmaceutical applications.