Coimmobilized Pyridoxal 5′-Phosphate and Aminotransferase in a Hydrogen-Bonded Organic Framework for Sustainable Synthesis of Sitagliptin

Aminotransferases (ATAs), essential enzymes for the synthesis of chiral amine drugs, play a crucial role in the synthesis of sitagliptin. The catalytic process of ATAs relies on the effective synergistic action of the cofactor pyridoxal 5′-phosphate (PLP). However, practical applications face challenges such as the poor stability of ATAs and the inefficient recovery of the expensive cofactor PLP. To address these issues, this study proposes a high-efficiency and stable catalytic nanoreactor, ATA&PLP@PAH-BioHOF-1, fabricated by polyelectrolyte poly(allylamine hydrochloride) (PAH)-mediated coencapsulation of both ATA and PLP in a hydrogen-bonded organic framework, BioHOF-1, for the synthesis of sitagliptin. This immobilization system overcomes the limitations of traditional single immobilization methods that were unable to simultaneously maintain enzyme activity and sustainably reuse the cofactor. The system exhibits excellent loading capacity and catalytic performance, achieving a sitagliptin yield of over 95% within 4 h. Additionally, the system demonstrates outstanding stability, retaining 78.3% of its initial sitagliptin yield (95%) after 18 consecutive catalytic cycles (4 h each), with a total PLP turnover number of 175. This study has thus provided an efficient nanoreactor system for the sustainable production of sitagliptin with in situ PLP recycling.