Efficient Synthesis of (S)-Nornicotine using Co-Immobilized IRED and GDH in Batch and Continuous Flow Reaction Systems

Nicotine is the chief addictive ingredient in cigarettes, cigars, and snuff, and has extensive applications in the agricultural and pharmaceutical industries. The synthesis of nicotine using free enzyme systems has been widely reported in literature; this approach chiefly utilizes the alkaloid myosmine and the enzymes imine reductase (IRED) as well as glucose dehydrogenase (GDH), and generates the intermediate (S)-nornicotine. Free enzymes are not reusable, thereby resulting in higher cost of production. The use of recyclable immobilized enzymes is an efficient approach for lowering the costs and improving the efficiency of production. In the current study, we present an efficient and environment-friendly approach utilizing immobilized enzymes for synthesizing (S)-nornicotine using batch and continuous flow reaction processes. A highly active coimmobilized enzyme system was successfully obtained by coimmobilizing IRED and GDH on the resin LXTE-706. The immobilized enzymes were amenable to repeated usage for at least 40 operation cycles in the batch mode of operation and yielded a product with a high chiral purity of >99.90%, effectively reducing the overall production cost. Furthermore, a space–time yield of 211.47 g/Lh was obtained using a continuous mode of operation, which is 289.7-fold higher than that obtained with batch mode.