Fatty acid chain modification of loxenatide and its kinetics in a continuous flow microchannel reactor. (January 2023)

• Record Type: Journal Article
• Authors: Wang, Shu-Chang; Wang, Xu-Dong; Teng, Xin-Nan; Dai, Jian-Ying; Dong, Yue-Sheng; Yuan, Heng-Li; Xiu, Zhi-Long
• Is Part Of: Process biochemistry. Volume 124(2023)
• Page Start: 259
• Page End: 268
• Publication Date: 2023-01
• Subjects: Fatty acid chain modification -- Loxenatide -- Microreactor -- Reaction kinetics; Biochemical engineering -- Periodicals; Biotechnology -- Periodicals; Biochemistry -- periodicals; Biotechnology -- periodicals; Chemical Engineering -- periodicals; Génie biochimique -- Périodiques; Biotechnologie -- Périodiques; Biochemical engineering; Biotechnology; Periodicals; 660.63
• DOI: 10.1016/j.procbio.2022.12.007
• Languages: English
• ISSNs: 1359-5113

Abstract

Abstract: In this study, a continuous flow microchannel reactor was designed and constructed for continuous and efficient fatty acid chain modification (FACylation) of polypeptides to achieve higher production capacity than that obtained in a batch reactor. In this microreactor, loxenatide (LOX) was site-specifically modified by N-tetradecylmaleimide (C14 -MAL) to continuously synthesize the target product, N-tetradecyl-loxenatide (C14 -LOX). Based on the experimental data under different conditions, a kinetic model of FACylation was established to describe the initial stage of the continuous reaction in the microreactor. Under the optimal conditions obtained by the kinetic model, the reaction time in the microreactor could be reduced to 1/3 that of the batch reactor at the same yield, and the production capacity of the microreactor was at least 3.78 times that of the batch reactor within the same time (40 h). These results would contribute to the development of microreactors in the biopharmaceutical industry. Graphical Abstract: ga1 Highlights: Loxenatide (LOX) was specifically modified by a fatty acid chain. Continuous and efficient synthesis of the product C14 -LOX by a microchannel reactor. The optimal reaction conditions obtained by the reaction kinetics.