Magnetic multi-enzymatic system for Cladribine manufacturing
dc.contributor.author | Cruz, Guillermo | |
dc.contributor.author | Saiz, Laura Pilar | |
dc.contributor.author | Bilal, Muhammad | |
dc.contributor.author | Eltoukhy, Lobna | |
dc.contributor.author | Loderer, Christoph | |
dc.contributor.author | Fernández Lucas, Jesús | |
dc.date.accessioned | 2024-10-10T15:27:13Z | |
dc.date.available | 2024-10-10T15:27:13Z | |
dc.date.issued | 2022-11 | |
dc.description.abstract | Enzyme-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.department | Depto. de Bioquímica y Biología Molecular | |
dc.description.faculty | Fac. de Ciencias Biológicas | |
dc.description.refereed | TRUE | |
dc.description.sponsorship | Ministerio de Ciencia e Innovación (España) | |
dc.description.sponsorship | National Science Centre | |
dc.description.sponsorship | Deutsche Forschungsgemeinschaft | |
dc.description.status | pub | |
dc.identifier.citation | Cruz, 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.doi | 10.3390/ijms232113634 | |
dc.identifier.issn | 1422-0067 | |
dc.identifier.officialurl | https://doi.org/10.3390/ijms232113634 | |
dc.identifier.relatedurl | https://www.mdpi.com/1422-0067/23/21/13634 | |
dc.identifier.uri | https://hdl.handle.net/20.500.14352/108867 | |
dc.issue.number | 21 | |
dc.journal.title | International Journal of Molecular Sciences | |
dc.language.iso | eng | |
dc.page.final | 13 | |
dc.page.initial | 1 | |
dc.publisher | MDPI | |
dc.relation.projectID | PID2020-117025RB-I00 | |
dc.relation.projectID | info:eu-repo/grantAgreement/NCN//2020%2F37%2FK%2FST8%2F03805 | |
dc.relation.projectID | info:eu-repo/grantAgreement/DFG//LO 2678%2F2-1 | |
dc.rights | Attribution 4.0 International | en |
dc.rights.accessRights | open access | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject.cdu | 577.15 | |
dc.subject.cdu | 577.2 | |
dc.subject.cdu | 60 | |
dc.subject.cdu | 661.12 | |
dc.subject.keyword | Cascade synthesis | |
dc.subject.keyword | Magnetic catalysts | |
dc.subject.keyword | Enzyme immobilization | |
dc.subject.keyword | Transglycosylation reaction | |
dc.subject.keyword | Nucleoside analogues | |
dc.subject.ucm | Bioquímica (Biología) | |
dc.subject.ucm | Biología molecular (Biología) | |
dc.subject.ucm | Biotecnología | |
dc.subject.ucm | Medicamentos | |
dc.subject.unesco | 2403 Bioquímica | |
dc.subject.unesco | 2415 Biología Molecular | |
dc.subject.unesco | 2302.09 Enzimología | |
dc.subject.unesco | 3302 Tecnología Bioquímica | |
dc.subject.unesco | 3209.01 Análisis de Medicamentos | |
dc.title | Magnetic multi-enzymatic system for Cladribine manufacturing | |
dc.type | journal article | |
dc.type.hasVersion | VoR | |
dc.volume.number | 23 | |
dspace.entity.type | Publication | |
relation.isAuthorOfPublication | f99cf5b4-0f0d-424c-afd9-77bdedffd366 | |
relation.isAuthorOfPublication.latestForDiscovery | f99cf5b4-0f0d-424c-afd9-77bdedffd366 |
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