An efficient biocatalytic system for floxuridine biosynthesis based on Lactobacillus animalis ATCC 35046 immobilized in Sr-alginate

作者：Cappa Valeria A; Rivero Cintia W; Britos Claudia N; Martinez Luis M; Lozano Mario E; Trelles Jorge A^*

来源：Process Biochemistry, 2014, 49(7): 1169-1175.

DOI：10.1016/j.procbio.2014.03.029

• Lactic acid bacteria
• Halogenated 2 '-deoxyribosides
• Microorganism stabilization
• Co-solvents
• Anti-tumoral compounds

An efficient and green immobilized biocatalyst is herein reported to obtain 5-fluorouracil-2'-deoxyriboside (5FUradRib), an antimetabolite known as Floxuridine, used in gastrointestinal cancer treatment.
Alginate is a natural polysaccharide used in the pharmaceutical industry due to its physicochemical properties, biocompatibility and non-toxicity. Multivalent cations, exposure time and cross-linking solution concentration were optimized, being Sr2+, 2 h and 0.2 M the best immobilization conditions. Furthermore, compression strength, swelling ratio and fracture frequency were evaluated, improving the mechanical stability of the biocatalyst favoring a future scale-up.
On the other hand, the reaction parameters for 5FUradRib biosynthesis were optimized in order to obtain an immobilized biocatalyst with enhanced activity. Thus, Lactobacillus animalis ATCC 35046 immobilized in Sr-alginate showed yields of 96% at short reaction times.
The obtained biocatalyst was stable for more than 25 days in storage conditions (4 C) and could be reused at least 10 times without loss of its activity.
Additionally, Sr-alginate biocatalyst stability was evaluated in different organic solvents to obtain hydrophobic compounds such as 5-bromouracil-2'-deoxyriboside (5BrUradRib), an effective radiosensitizing agent used in anti-cancer therapy, being hexane the best co-solvent.
Finally, a smooth, cheap and environmentally friendly method to obtain anti-cancer drugs was developed in this study.

• 出版日期2014-7