Design of a ceramic monolith millireactor for enzymatic resveratrol dimerization using an immobilized GOx-HRP cascade

Enzymatic oxidative dimerization of resveratrol offers a sustainable method for synthesizing structurally complex bioactive stilbene derivatives under mild reaction conditions. Horseradish peroxidase (HRP) is an effective biocatalyst for these transformations; however, its activity is highly dependent on hydrogen peroxide concentration. Excess hydrogen peroxide leads to rapid enzyme deactivation, while insufficient amounts result in low reaction rates and poor conversion. To address these challenges, enzyme cascade systems based on glucose oxidase (GOx) have been developed, in which hydrogen peroxide is generated in situ by oxidizing glucose with dissolved oxygen as the substrate. This strategy allows for controlled peroxide generation and improved HRP stability, but introduces a new challenge related to efficient oxygen supply and gas-liquid mass transfer. In this study, a novel ceramic monolith millireactor is proposed for immobilizing GOx and HRP and enabling continuous enzymatic dimerization of resveratrol. Ceramic monoliths offer a high specific surface area, excellent mechanical and chemical stability, and favourable conditions for enzyme immobilization while maintaining a low pressure drop. Impact of monolith geometry and enhanced surface structures are evaluated to maximize enzyme loading and improve oxygen availability within the reactor. Particular attention is given to oxygen management strategies to prevent bubble formation and mass-transfer limitations commonly seen in conventional aerated microreactor systems. The proposed reactor design combines biocatalyst immobilization and controlled oxygen delivery within a single process intensification platform. This system is expected to enable stable operation of the GOx-HRP cascade, efficient in situ hydrogen peroxide generation, and improved resveratrol dimerization performance.