Magnetic Multi-Enzymatic System for Cladribine Manufacturing

  1. Cruz, Guillermo
  2. Saiz, Laura Pilar
  3. Bilal, Muhammad
  4. Eltoukhy, Lobna
  5. Loderer, Christoph
  6. Fernández-Lucas, Jesús
  1. 1 Universidad Europea de Madrid
    info

    Universidad Europea de Madrid

    Madrid, España

    ROR https://ror.org/04dp46240

  2. 2 Poznań University of Technology
    info

    Poznań University of Technology

    Posnania, Polonia

    ROR https://ror.org/00p7p3302

  3. 3 Dresden University of Technology
    info

    Dresden University of Technology

    Dresde, Alemania

    ROR https://ror.org/042aqky30

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Revista:
International Journal of Molecular Sciences

ISSN: 1422-0067

Año de publicación: 2022

Volumen: 23

Número: 21

Páginas: 13634

Tipo: Artículo

DOI: 10.3390/IJMS232113634 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: International Journal of Molecular Sciences

Resumen

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.

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Referencias bibliográficas

  • Fernández-Lucas, J., and Camarasa, M.J. Enzymatic and Chemical Synthesis of Nucleic acid Derivatives, 2019.
  • Simić, (2021), Chem. Rev., 122, pp. 1052, 10.1021/acs.chemrev.1c00574
  • Wu, (2021), Angew. Chem. Int. Ed., 60, pp. 88, 10.1002/anie.202006648
  • Lapponi, (2016), J. Mol. Catal. B Enzym., 133, pp. 218, 10.1016/j.molcatb.2016.08.015
  • Del Arco, (2021), Biotechnol. Adv., 51, pp. 107701, 10.1016/j.biotechadv.2021.107701
  • Mikhailopulo, (2010), Acta Nat., 2, pp. 36, 10.32607/20758251-2010-2-2-36-58
  • Lewkowicz, (2017), Curr. Pharm. Des., 23, pp. 6851, 10.2174/1381612823666171011101133
  • Rinaldi, (2020), Bioresour. Technol., 307, pp. 123258, 10.1016/j.biortech.2020.123258
  • Kamel, (2018), Mol. Catal., 458, pp. 52, 10.1016/j.mcat.2018.07.028
  • Fresco-Taboada, (2013), Appl. Microbiol. Biotechnol., 97, pp. 3773, 10.1007/s00253-013-4816-y
  • Del Arco, (2017), Curr. Pharm. Des., 23, pp. 6898, 10.2174/1381612823666171017165707
  • Del Arco, (2017), Food Chem., 237, pp. 605, 10.1016/j.foodchem.2017.05.136
  • Del Arco, (2019), Bioresour. Technol., 276, pp. 244, 10.1016/j.biortech.2018.12.120
  • Mikhailopulo, (2011), Mendeleev Commun., 21, pp. 57, 10.1016/j.mencom.2011.03.001
  • Frisch, J., Maršić, T., and Loderer, C. A novel one-pot enzyme cascade for the biosynthesis of cladribine triphosphate. Biomolecules, 2021. 11.
  • Ding, (2020), Appl. Biochem. Biotechnol., 190, pp. 1271, 10.1007/s12010-019-03138-3
  • Spurgeon, (2002), Expert Opin. Investig. Drugs, 18, pp. 1169, 10.1517/13543780903071038
  • Biernacki, (2020), Mini Rev. Med. Chem., 20, pp. 269, 10.2174/1389557519666191015201755
  • Britos, (2016), J. Fluor. Chem., 186, pp. 91, 10.1016/j.jfluchem.2016.04.012
  • Drenichev, (2018), Adv. Synth. Catal., 360, pp. 305, 10.1002/adsc.201701005
  • Liu, G., Cheng, T., Chu, J., Li, S., and He, B. Efficient synthesis of purine nucleoside analogs by a new trimeric purine nucleoside phosphorylase from Aneurinibacillus migulanus AM007. Molecules, 2020. 25.
  • Rabuffetti, M., Bavaro, T., Semproli, R., Cattaneo, G., Massone, M., Morelli, C.F., Speranza, G., and Ubiali, D. Synthesis of ribavirin, tecadenoson, and cladribine by enzymatic transglycosylation. Catalysts, 2019. 9.
  • Zhou, (2015), Adv. Synth. Catal., 357, pp. 1237, 10.1002/adsc.201400966
  • Acosta, J., Del Arco, J., Martinez-Pascual, S., Clemente-Suárez, V.J., and Fernández-Lucas, J. One-pot multi-enzymatic production of purine derivatives with application in pharmaceutical and food industry. Catalysts, 2018. 8.
  • Pérez, (2018), ChemCatChem, 10, pp. 4406, 10.1002/cctc.201800775
  • Rivero, C.W., García, N.S., Fernández-Lucas, J., Betancor, L., Romanelli, G.P., and Trelles, J. Green production of cladribine by using immobilized 2′-deoxyribosyltransferase from Lactobacillus delbrueckii stabilized through a double covalent/entrapment technology. Biomolecules, 2021. 11.
  • Sheldon, (2013), Chem. Soc. Rev., 42, pp. 6223, 10.1039/C3CS60075K
  • Mateo, (2007), Enzyme Microb. Technol., 40, pp. 1451, 10.1016/j.enzmictec.2007.01.018
  • Barbosa, (2013), Biomacromolecules, 14, pp. 2433, 10.1021/bm400762h
  • Fresco-Taboada, A., Fernández-Lucas, J., Acebal, C., Arroyo, M., Ramón, F., De la Mata, I., and Mancheño, J.M. 2′-Deoxyribosyltransferase from Bacillus psychrosaccharolyticus: A mesophilic-like biocatalyst for the synthesis of modified nucleosides from a psychrotolerant bacterium. Catalysts, 2018. 8.
  • Borlido, (2013), Biotechnol. Adv., 31, pp. 1374, 10.1016/j.biotechadv.2013.05.009
  • Del Arco, (2021), Bioresour. Technol., 322, pp. 124547, 10.1016/j.biortech.2020.124547
  • Crespo, (2017), Appl. Microbiol. Biotechnol., 101, pp. 7187, 10.1007/s00253-017-8450-y
  • Guddat, (2002), Prot. Sci., 11, pp. 1626, 10.1110/ps.0201002
  • Keough, (2013), J. Med. Chem., 56, pp. 6967, 10.1021/jm400779n
  • Acosta, (2021), Bioresour. Technol., 339, pp. 125649, 10.1016/j.biortech.2021.125649
  • Del Arco, (2019), Bioresour. Technol., 289, pp. 121772, 10.1016/j.biortech.2019.121772
  • Fernández-Lucas, (2011), Appl. Microbiol. Biotechnol., 91, pp. 317, 10.1007/s00253-011-3221-7
  • Fernández-Lucas, (2012), Bioresour. Technol., 115, pp. 63, 10.1016/j.biortech.2011.11.127
  • Fernández-Lucas, (2013), J. Ind. Microbiol. Biotechnol., 40, pp. 955, 10.1007/s10295-013-1304-4
  • Fresco-Taboada, (2014), Molecules, 19, pp. 11231, 10.3390/molecules190811231
  • Fresco-Taboada, (2016), Catal. Today, 259, pp. 197, 10.1016/j.cattod.2015.06.032
  • Del Arco, J., Martínez-Pascual, S., Clemente-Suárez, V.J., Corral, O.J., Jordaan, J., Hormigo, D., Perona, A., and Fernández-Lucas, J. One-pot, one-step production of dietary nucleotides by magnetic biocatalysts. Catalysts, 2018. 8.
  • Rodrigues, (2013), Chem. Soc. Rev., 42, pp. 6290, 10.1039/C2CS35231A
  • Santos, (2015), Chem. Cat. Chem., 7, pp. 2413
  • Behrens, (2011), Angew. Chem. Int. Ed., 50, pp. 2220, 10.1002/anie.201002094
  • Acosta, J., Pérez, E., Sánchez-Murcia, P.A., Fillat, C., and Fernández-Lucas, J. Molecular basis of NDT-mediated activation of nucleoside-based prodrugs and application in suicide gene therapy. Biomolecules, 2021. 11.