Sustainable production of nucleoside analogues by a high-efficient purine 2′- deoxyribosyltransferase immobilized onto Ni2+ chelate magnetic microparticles

The present work aims to develop a magnetic biocatalyst for customized production of nucleoside analogues using mutant His-tagged purine 2′-deoxyribosyltransferase from Trypanosoma brucei (TbPDTV11S) immobilized onto Ni2+ chelate magnetic iron oxide porous microparticles (MTbPDTV11S). Biochemical ch...

Full description

Autores:
Del Arco, Jon
Jordaan, Justin
Moral Dardé, Verónica
Fernández Lucas, Jesús
Tipo de recurso:
Article of investigation
Fecha de publicación:
2019
Institución:
Corporación Universidad de la Costa
Repositorio:
REDICUC - Repositorio CUC
Idioma:
eng
OAI Identifier:
oai:repositorio.cuc.edu.co:11323/10739
Acceso en línea:
https://hdl.handle.net/11323/10739
https://repositorio.cuc.edu.co/
Palabra clave:
Enzyme immobilization
Bioprocesses
Nucleoside analogues
2′-Deoxyribosyltransferases
Rights
openAccess
License
Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
Description
Summary:The present work aims to develop a magnetic biocatalyst for customized production of nucleoside analogues using mutant His-tagged purine 2′-deoxyribosyltransferase from Trypanosoma brucei (TbPDTV11S) immobilized onto Ni2+ chelate magnetic iron oxide porous microparticles (MTbPDTV11S). Biochemical characterization revealed MTbPDTV11S5 as optimal candidate for further studies (10,552 IU g−1; retained activity 54% at 50 °C and pH 6.5). Interestingly, MTbPDTV11S5 displayed the highest activity value described up to date for an immobilized NDT. Moreover, MTbPDTV11S5 was successfully employed in the one-pot, one-step production of different therapeutic nucleoside analogues, such as cladribine or 2′-deoxy-2-fluoroadenosine, among others. Finally, MTbPDTV11S5 proved to be stable when stored at 50 °C for 8 h and pH 6.0 and reusable up to 10 times without negligible loss of activity in the enzymatic production of the antitumor prodrug 2′-deoxy-2-fluoroadenosine.