The operation of enzyme cascades in microfluidic devices is a current field of research that promises manifold applications in biocatalysis. For an optimization of flow biocatalysis systems it is desirable to model the reactor in silico in order to enable a better understanding and thus an economic optimization of the reaction systems. However, due to their high complexity, it is still difficult to simulate coupled enzyme reactions. We here describe a new model for a plug flow reactor consisting of a porous bed of compact uniform particles functionalized with an immobilized ketoreductase (Gre2) which is overflown by a mobile phase containing the enzymatic NADPH cofactor regeneration system based on glucose dehydrogenase (GDH). By studying different flow rates, lengths and layer thicknesses of the catalytic bed, we show that the synergy of experiment and mathematical modeling can optimize the space-time yields of the reaction system.

Mit einem Fokusthema „Flexible Production #FlexProd” stellte die ACHEMA in diesem Jahr Anlagenkonzepte für eine digitalisierte, agile und adaptive Prozessindustrie zum allgemeinen Industrietrend Industrie 4.0 in den Vordergrund. Eine tragende Säule dieses Fokusthemas war der Flow Chemistry Pavillion. Dieser Ausstellungsteil bündelte auf einer weitläufigen Ausstellungsfläche innovative Aussteller zur kontinuierlichen Produktion samt Präsentations‐ und Diskussionsbereich. Die aktuellen Trends und Produkte aus der Mikroverfahrenstechnik werden vorgestellt, die die Zukunft der Mikroverfahrenstechnik bahnen sollen.

Immobilized multi-enzyme cascades are increasingly used in microfluidic devices. In particular, their application in continuous flow reactors shows great potential, utilizing the benefits of reusability and control of the reaction conditions. However, capitalizing on this potential is challenging and requires detailed knowledge of the investigated system. Here, we show the application of computational methods for optimization with multi-level reactor design (MLRD) methodology based on the underlying physical and chemical processes. We optimize a stereoselective reduction of a diketone catalyzed by ketoreductase (Gre2) and Nicotinamidadenindinukleotidphosphat (NADPH) cofactor regeneration with glucose dehydrogenase (GDH). Both enzymes are separately immobilized on magnetic beads forming a packed bed within the microreactor. We derive optimal reactor feed concentrations and enzyme ratios for enhanced performance and a basic economic model in order to maximize the techno-economic performance (TEP) for the first reduction of 5-nitrononane-2,8-dione.