A novel continuous flow biosynthesis of caffeic acid phenethyl ester from alkyl caffeate and phenethanol in a packed bed microreactor

Caffeic acid phenethyl ester (CAPE) is a rare natural ingredient with several biological activity, but the industrial production of CAPE using lipase-catalyzed esterification of caffeic acid (CA) and 2-phenylethanol (PE) in ionic liquids is hindered by low substrate concentrations and a long reaction time. To establish a high-efficiency bioprocess for obtaining CAPE, a novel continuous flow biosynthesis of CAPE from alkyl caffeate and PE in [Bmim][Tf2N] using a packed bed microreactor was successfully carried out. Among the tested alkyl caffeates and lipases, methyl caffeate and Novozym 435, respectively, were selected as the suitable substrate and biocatalyst. Under the optimum conditions selected using response surface methodology, a 93.21% CAPE yield was achieved in 2.5 h using a packed bed microreactor, compared to 24 h using a batch reactor. The reuse of Novozym 435 for 20 cycles and continuous reaction for 9 days did not result in any decrease in activity.