A novel thymidine phosphorylase to synthesize (halogenated) anticancer and antiviral nucleoside drugs in continuous flow.

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 p

SUBMITTER: Benitez-Mateos AI 

PROVIDER: S-EPMC9575728 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature