Immobilized enzyme reactors based on nucleoside phosphorylases and 2′-deoxyribosyltransferase for the in-flow synthesis of pharmaceutically relevant nucleoside analogues

In this work, a mono- and a bi-enzymatic analytical immobilized enzyme reactors (IMERs) were developed as prototypes for biosynthetic purposes and their performances in the in-flow synthesis of nucleoside analogues of pharmaceutical interest were evaluated. Two biocatalytic routes based on nucleosid...

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Autores:
Rinaldia, Francesca
Fernández-Lucas, Jesús
de la Fuente, Diego
Zheng, Changping
Teodora Bavaro
BAVARO, TEODORA
Peters, Benjamin
MASSOLINI, GABRIELLA
Contig, Paola
de la Mata, Isabel
TERRENI, MARCO
Calleri, Enrica
Tipo de recurso:
http://purl.org/coar/resource_type/c_816b
Fecha de publicación:
2020
Institución:
Corporación Universidad de la Costa
Repositorio:
REDICUC - Repositorio CUC
Idioma:
eng
OAI Identifier:
oai:repositorio.cuc.edu.co:11323/6247
Acceso en línea:
https://hdl.handle.net/11323/6247
https://doi.org/10.1016/j.biortech.2020.123258
https://repositorio.cuc.edu.co/
Palabra clave:
Biocatalysis
Immobilized enzyme reactors
Nucleoside analogues
Nucleoside 2′-deoxyribosyltransferases
Nucleoside phosphorylases
Rights
openAccess
License
CC0 1.0 Universal
Description
Summary:In this work, a mono- and a bi-enzymatic analytical immobilized enzyme reactors (IMERs) were developed as prototypes for biosynthetic purposes and their performances in the in-flow synthesis of nucleoside analogues of pharmaceutical interest were evaluated. Two biocatalytic routes based on nucleoside 2′-deoxyribosyltransferase from Lactobacillus reuteri (LrNDT) and uridine phosphorylase from Clostridium perfrigens (CpUP)/purine nucleoside phosphorylase from Aeromonas hydrophila (AhPNP) were investigated in the synthesis of 2′-deoxy, 2′,3′-dideoxy and arabinonucleoside derivatives. LrNDT-IMER catalyzed the synthesis of 5-fluoro-2′-deoxyuridine and 5-iodo-2′-deoxyuridine in 65–59% conversion yield, while CpUP/AhPNP-IMER provided the best results for the preparation of arabinosyladenine (60% conversion yield). Both IMERs proved to be promising alternatives to chemical routes for the synthesis of nucleoside analogues. The developed in-flow system represents a powerful tool for the fast production on analytical scale of nucleosides for preliminary biological tests.