Use of Citrobacter koseri whole cells for the production of arabinonucleosides: A larger scale approach

► C. koseri cells catalyzed the transglycosylation of arabinonucleosides. ► Fludarabine, vidarabine and diaminopurine arabinoside were obtained in good yields. ► Different entrapment immobilizations and reactor configurations were assayed. ► C. koseri immobilized in agarose could be used up to 68 ti...

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Bibliographic Details
Published in:Process biochemistry (1991) 2012-12, Vol.47 (12), p.2182-2188
Main Authors: Nóbile, Matías, Médici, Rosario, Terreni, Marco, Lewkowicz, Elizabeth S., Iribarren, Adolfo M.
Format: Article
Language:English
Subjects:
agarose
antineoplastic agents
biocatalysts
biotransformation
Citrobacter
Citrobacter koseri
Drugs
Expansion
Fludarabine
Immobilized biocatalysts
industrial applications
Microorganisms
Nucleosides
Purines
screening
storage quality
Synthesis
Transformations
Transglycosylation
Vidarabine
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Summary:► C. koseri cells catalyzed the transglycosylation of arabinonucleosides. ► Fludarabine, vidarabine and diaminopurine arabinoside were obtained in good yields. ► Different entrapment immobilizations and reactor configurations were assayed. ► C. koseri immobilized in agarose could be used up to 68 times. ► 150mL scale reaction afforded vidarabine in 71.2% yield. Purine arabinosides are well known antiviral and antineoplastic drugs. Since their chemical synthesis is complex, time-consuming, and polluting, enzymatic synthesis provides an advantageous alternative. In this work, we describe the microbial whole cell synthesis of purine arabinosides through nucleoside phosphorylase-catalyzed transglycosylation starting from their pyrimidine precursors. By screening of our microbial collection, Citrobacter koseri (CECT 856) was selected as the best biocatalyst for the proposed biotransformation. In order to enlarge the scale of the transformations to 150mL for future industrial applications, the biocatalyst immobilization by entrapment techniques and its behavior in different reactor configurations, considering both batch and continuous processes, were analyzed. C. koseri immobilized in agarose could be used up to 68 times and the storage stability was at least 9 months. By this approach, fludarabine (58% yield in 14h), vidarabine (71% yield in 26h) and 2,6-diaminopurine arabinoside (77% yield in 24h), were prepared.
ISSN:1359-5113
1873-3298
DOI:10.1016/j.procbio.2012.08.011