Enzyme‐Catalyzed Synthesis of Nonnatural or Modified Nucleosides

Abstract

Nucleosides and their analogs possess several pharmacological activities, so that many strategies have been developed in order to prepare these compounds. The chemical synthesis of these labile and polyfunctional molecules is very complex because many protection–deprotection steps are involved in their preparation. In this sense, biocatalyzed synthesis of nucleosides using either whole cells or enzymes is a greener alternative to conventional methodologies; not only are the number of synthetic steps reduced, but also the waste production is minimized, while the required solvents are environment‐friendly. Some new enzymes, showing different specificities, have become available in recent years. In fact, advances in fermentation, purification, and immobilization techniques have resulted in the production of more stable biocatalysts at significantly reduced cost. Automated screening, new metagenomic techniques, directed evolution, and metabolic engineering have led to the production of novel customized industrial enzymes. For those reasons, there are a large number of patents in Europe and United States of America that are related to these advances. In the present review, we describe many examples used at laboratory scale, and some industrial applications that are not that extensively implemented now will also be commented on. Nevertheless, new scientific developments promise to overcome these drawbacks in the near future.

Development of an immobilized biocatalyst based on Bacillus psychrosaccharolyticus NDT for the preparative synthesis of trifluridine and decytabine

“…The use of glycosyl-transferring enzymes applied to the synthesis of modified nucleosides is an established procedure endowed with several advantages over the traditional multistep chemical methods [1][2][3]. These advantages arise from the inherent properties of enzymes such as stereo-, regio-, enantiospecificity and mild reaction conditions.…”

Green biosynthesis of floxuridine by immobilized microorganisms

“…Biosynthesis of purine nucleoside analogues by transglycosylation has been extensively studied (Sinisterra et al, 2010). However, there have been few reports about obtaining pyrimidine nucleosides halogenated on the base moiety using whole cells.…”