Study on the Immobilization of a Transaminase Biocatalyst for the Synthesis of Sitagliptin

Sitagliptin, an important anti-diabetic drug, can be obtained using transaminase (TA) enzymes, which are known to be promising biocatalysts for the production of highly enantiopure amines under mild reaction conditions. In an industrial context, the use of immobilized enzymes can provide several advantages, such as the improved stability of the biocatalyst and easy product recovery. In this study, a new commercially available transaminase enzyme to produce sitagliptin was immobilized on inorganic and organic supports using two different approaches: adsorption and covalent bond formation. Among the inorganic media, non-functionalized silica gel was chosen for its stability and competitive cost. A range of commercially available resins with different functionalities have also been selected for their characteristics that can meet industrial standards. The immobilized biocatalysts were first tested in the transamination of acetophenone as a model substrate, which obtains, in most cases, higher conversions with respect to soluble enzymes. The best results in the enantioselective synthesis of sitagliptin were achieved with the sample immobilized on the epoxy- and octadecyl-functionalized methacrylic resin, which allowed the complete conversion of the corresponding ketone and high enantioselectivity (>99% ee). Moreover, the recycling of the supported enzyme could be performed in a continuous flow system without loss of activity for five consecutive runs.