Green biosynthesis of floxuridine by immobilized microorganisms

Abstract

This work describes an efficient, simple, and green bioprocess for obtaining 5‐halogenated pyrimidine nucleosides from thymidine by transglycosylation using whole cells. Biosynthesis of 5‐fluoro‐2′‐deoxyuridine (floxuridine) was achieved by free and immobilized Aeromonas salmonicida ATCC 27013 with an 80% and 65% conversion occurring in 1 h, respectively. The immobilized biocatalyst was stable for more than 4 months in storage conditions (4 °C) and could be reused at least 30 times without loss of its activity. This microorganism was able to biosynthesize 2.0 mg L−1 min−1 (60%) of 5‐chloro‐2′‐deoxyuridine in 3 h. These halogenated pyrimidine 2′‐deoxynucleosides are used as antitumoral agents.

Efficient Biocatalytic Synthesis of Dihalogenated Purine Nucleoside Analogues Applying Thermodynamic Calculations

“…Besides the optimization of the enzymatic synthesis process by thermodynamic calculation, the present study also investigated the impact of a chlorine atom at position 6 of the nucleoside with respect to its inhibitory effect on leukemic cells. This was based on the observation that halogenation is an important prerequisite for anticancer activity [3,23,24], since amino groups make the compound susceptible to deamination by adenosine deaminase (ADA) [25,26]. The addition of a chlorine or fluorine atom in position 2 of adenosine strongly increased its stability, as observed for the very potent leukemia drugs cladribine and fludarabine [23,26].…”

“…Due to the drawbacks of chemical synthesis routes, alternative methods have been developed. Enzymatic synthesis is environmentally more friendly, highly selective, and efficient [3]. The most commonly applied enzyme-catalyzed reaction for the preparation of nucleosides and their analogues is the one-pot transglycosylation with pyrimidine and purine nucleoside phosphorylases [4].…”

Bioproduction of ribavirin by green microbial biotransformation

“…Biocatalyst stabilization 2.5.1. Matrix selection E. coli ATCC 12407 was immobilized by entrapment in agar gracilaria 3% (w/v), agar gelidium 3% (w/v), agarose 3% (w/v) and polyacrylamide 20% (w/v) as described by Rivero et al [14].…”

Bioproduction of Floxuridine Using Nanostabilized Biocatalysts

“…This modified nucleoside is mainly synthesized by chemical methods, however, its biocatalytic synthesis using microorganisms is a promising alternative 3. Nevertheless, the application of microorganisms in soluble form is limited by their low stability 4. Currently, different immobilization techniques have allowed to stabilize biocatalysts, facilitating their reusability, favoring their biocatalytic activity and bioprocess scale‐up 5.…”