A novel thymidine phosphorylase to synthesize (halogenated) anticancer and antiviral nucleoside drugs in continuous flow. Issue 20 (15th September 2022)

• Record Type: Journal Article
• Authors: Benítez-Mateos, Ana I.; Klein, Calvin; Roura Padrosa, David; Paradisi, Francesca
• Is Part Of: Catalysis science & technology. Volume 12:Issue 20(2022)
• Page Start: 6231
• Page End: 6238
• Publication Date: 2022-09-15
• Subjects: Catalysis -- Periodicals; 541.395
• DOI: 10.1039/d2cy00751g
• Languages: English
• ISSNs: 2044-4753

Abstract

Abstract : A novel thymidine phosphorylase from H. elongata has been characterized, immobilized, and applied in a flow reactor. With this biocatalyst, four halogenated nucleoside analogues with anticancer and antiviral properties were produced in high yields. Abstract : Four pharmaceutically relevant nucleoside analogues (5-fluoro-2′-deoxyuridine, 5-chloro-2′-deoxyuridine, 5-bromo-2′-deoxyuridine, and 5-iodo-2′-deoxyuridine) have been synthesized by using a novel thymidine phosphorylase from the halotolerant H. elongata (HeTP). Following enzyme immobilization on microbeads, the biocatalyst was implemented as a packed-bed reactor for the continuous production of halogenated nucleosides, achieving up to 90% conversion at the 10 mM scale with 30 min residence time. Taking the synthesis of floxuridine (5-fluoro-2′-deoxyuridine) as a study case, we obtained the highest space–time yield (5.5 g L −1 h −1 ) reported to date. In addition, bioinformatic tools such as MD analysis and CapiPy have contributed to shine light on the catalytic performance of HeTP as well as its immobilization, respectively.