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2'-Deoxyribosyltransferase from Leishmania mexicana, an efficient biocatalyst for one-pot, one-step synthesis of nucleosides from poorly soluble purine bases

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dc.contributor.author Crespo, Noé
dc.contributor.author Sánchez-Murcia, Pedro A.
dc.contributor.author Gago, Federico
dc.contributor.author Cejudo Sanches, Janaina
dc.contributor.author Galmes, Miguel Angel
dc.contributor.author Fernández Lucas, Jesús
dc.contributor.author Mancheño, José Miguel
dc.date.accessioned 2017-09-04T09:47:18Z
dc.date.available 2017-09-04T09:47:18Z
dc.date.issued 2017-08-01
dc.identifier.citation Crespo, N., Sánchez-Murcia, P. A., Gago, F., Cejudo-Sanches, J., Galmes, M. A., Fernández-Lucas, J., & Mancheño, J. M. (2017). 2′-Deoxyribosyltransferase from Leishmania mexicana, an efficient biocatalyst for one-pot, one-step synthesis of nucleosides from poorly soluble purine bases. Applied Microbiology and Biotechnology, 1-14. spa
dc.identifier.issn 01757598
dc.identifier.uri http://hdl.handle.net/11268/6579
dc.description.abstract Processes catalyzed by enzymes offer numerous advantages over chemical methods although in many occasions the stability of the biocatalysts becomes a serious concern. Traditionally, synthesis of nucleosides using poorly water-soluble purine bases, such as guanine, xanthine, or hypoxanthine, requires alkaline pH and/or high temperatures in order to solubilize the substrate. In this work, we demonstrate that the 2′-deoxyribosyltransferase from Leishmania mexicana (LmPDT) exhibits an unusually high activity and stability under alkaline conditions (pH 8–10) across a broad range of temperatures (30–70 °C) and ionic strengths (0–500 mM NaCl). Conversely, analysis of the crystal structure of LmPDT together with comparisons with hexameric, bacterial homologues revealed the importance of the relationships between the oligomeric state and the active site architecture within this family of enzymes. Moreover, molecular dynamics and docking approaches provided structural insights into the substrate-binding mode. Biochemical characterization of LmPDT identifies the enzyme as a type I NDT (PDT), exhibiting excellent activity, with specific activity values 100- and 4000-fold higher than the ones reported for other PDTs. Interestingly, LmPDT remained stable during 36 h at different pH values at 40 °C. In order to explore the potential of LmPDT as an industrial biocatalyst, enzymatic production of several natural and non-natural therapeutic nucleosides, such as vidarabine (ara A), didanosine (ddI), ddG, or 2′-fluoro-2′-deoxyguanosine, was carried out using poorly water-soluble purines. Noteworthy, this is the first time that the enzymatic synthesis of 2′-fluoro-2′-deoxyguanosine, ara G, and ara H by a 2′-deoxyribosyltransferase is reported 2'-Deoxyribosyltransferase from Leishmania mexicana, an efficient biocatalyst for one-pot, one-step synthesis of nucleosides from poorly soluble purine bases. spa
dc.description.sponsorship Fundación Santander, Universidad Europea spa
dc.language.iso eng spa
dc.title 2'-Deoxyribosyltransferase from Leishmania mexicana, an efficient biocatalyst for one-pot, one-step synthesis of nucleosides from poorly soluble purine bases spa
dc.type article spa
dc.description.impact 3.420 JCR (2016) Q2, 43/158 Biotechnology and applied microbiology spa
dc.identifier.doi 10.1007/s00253-017-8450-y
dc.rights.accessRights closedAccess spa
dc.subject.uem Enzimas spa
dc.subject.uem Leishmaniosis spa
dc.subject.unesco Enzima spa
dc.subject.unesco Proteína spa
dc.description.filiation UEM spa


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