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Magnetic multi-enzymatic system for Cladribine manufacturing

dc.contributor.authorCruz, Guillermo
dc.contributor.authorSaiz, Laura Pilar
dc.contributor.authorBilal, Muhammad
dc.contributor.authorEltoukhy, Lobna
dc.contributor.authorLoderer, Christoph
dc.contributor.authorFernández Lucas, Jesús
dc.date.accessioned2024-10-10T15:27:13Z
dc.date.available2024-10-10T15:27:13Z
dc.date.issued2022-11
dc.description.abstractEnzyme-mediated processes have proven to be a valuable and sustainable alternative to traditional chemical methods. In this regard, the use of multi-enzymatic systems enables the realization of complex synthetic schemes, while also introducing a number of additional advantages, including the conversion of reversible reactions into irreversible processes, the partial or complete elimination of product inhibition problems, and the minimization of undesirable by-products. In addition, the immobilization of biocatalysts on magnetic supports allows for easy reusability and streamlines the downstream process. Herein we have developed a cascade system for cladribine synthesis based on the sequential action of two magnetic biocatalysts. For that purpose, purine 2′-deoxyribosyltransferase from Leishmania mexicana (LmPDT) and Escherichia coli hypoxanthine phosphoribosyltransferase (EcHPRT) were immobilized onto Ni2+-prechelated magnetic microspheres (MagReSyn®NTA). Among the resulting derivatives, MLmPDT3 (activity: 11,935 IU/gsupport, 63% retained activity, operational conditions: 40 °C and pH 5–7) and MEcHPRT3 (12,840 IU/gsupport, 45% retained activity, operational conditions: pH 5–8 and 40–60 °C) emerge as optimal catalysts for further synthetic application. Moreover, the MLmPDT3/MEcHPRT3 system was biochemically characterized and successfully applied to the one-pot synthesis of cladribine under various conditions. This methodology not only displayed a 1.67-fold improvement in cladribine synthesis (compared to MLmPDT3), but it also implied a practically complete transformation of the undesired by-product into a high-added-value product (90% conversion of Hyp into IMP). Finally, MLmPDT3/MEcHPRT3 was reused for 16 cycles, which displayed a 75% retained activity.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Ciencia e Innovación (España)
dc.description.sponsorshipNational Science Centre
dc.description.sponsorshipDeutsche Forschungsgemeinschaft
dc.description.statuspub
dc.identifier.citationCruz, Guillermo, et al. «Magnetic Multi-Enzymatic System for Cladribine Manufacturing». International Journal of Molecular Sciences, vol. 23, n.o 21, noviembre de 2022, p. 13634. DOI.org (Crossref), https://doi.org/10.3390/ijms232113634.
dc.identifier.doi10.3390/ijms232113634
dc.identifier.issn1422-0067
dc.identifier.officialurlhttps://doi.org/10.3390/ijms232113634
dc.identifier.relatedurlhttps://www.mdpi.com/1422-0067/23/21/13634
dc.identifier.urihttps://hdl.handle.net/20.500.14352/108867
dc.issue.number21
dc.journal.titleInternational Journal of Molecular Sciences
dc.language.isoeng
dc.page.final13
dc.page.initial1
dc.publisherMDPI
dc.relation.projectIDPID2020-117025RB-I00
dc.relation.projectIDinfo:eu-repo/grantAgreement/NCN//2020%2F37%2FK%2FST8%2F03805
dc.relation.projectIDinfo:eu-repo/grantAgreement/DFG//LO 2678%2F2-1
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu577.15
dc.subject.cdu577.2
dc.subject.cdu60
dc.subject.cdu661.12
dc.subject.keywordCascade synthesis
dc.subject.keywordMagnetic catalysts
dc.subject.keywordEnzyme immobilization
dc.subject.keywordTransglycosylation reaction
dc.subject.keywordNucleoside analogues
dc.subject.ucmBioquímica (Biología)
dc.subject.ucmBiología molecular (Biología)
dc.subject.ucmBiotecnología
dc.subject.ucmMedicamentos
dc.subject.unesco2403 Bioquímica
dc.subject.unesco2415 Biología Molecular
dc.subject.unesco2302.09 Enzimología
dc.subject.unesco3302 Tecnología Bioquímica
dc.subject.unesco3209.01 Análisis de Medicamentos
dc.titleMagnetic multi-enzymatic system for Cladribine manufacturing
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number23
dspace.entity.typePublication
relation.isAuthorOfPublicationf99cf5b4-0f0d-424c-afd9-77bdedffd366
relation.isAuthorOfPublication.latestForDiscoveryf99cf5b4-0f0d-424c-afd9-77bdedffd366

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