Characterization Of An Atypical, Thermostable, Organic Solvent- And Acid-Tolerant 2′-Deoxyribosyltransferase From Chroococcidiopsis Thermalis

In our search for thermophilic and acid-tolerant nucleoside 2′-deoxyribosyltransferases (NDTs), we found a good candidate in an enzyme encoded by Chroococcidiopsis thermalis PCC 7203 (CtNDT). Biophysical and biochemical characterization revealed CtNDT as a homotetramer endowed with good activity and...

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Autores:
Del Arco, Jon
Sánchez Murcia, Pedro Alejandro
Mancheño José Miguel, José Miguel
Gago, Federico
Fernandez Lucas, Jesus
Tipo de recurso:
Article of journal
Fecha de publicación:
2018
Institución:
Corporación Universidad de la Costa
Repositorio:
REDICUC - Repositorio CUC
Idioma:
eng
OAI Identifier:
oai:repositorio.cuc.edu.co:11323/1093
Acceso en línea:
https://hdl.handle.net/11323/1093
https://repositorio.cuc.edu.co/
Palabra clave:
Enzymatic Synthesis
Extremophiles
Homology Modeling
Nucleoside 2′-Deoxyribosyltransferase
Nucleoside Analogues
Rights
openAccess
License
Atribución – No comercial – Compartir igual
Description
Summary:In our search for thermophilic and acid-tolerant nucleoside 2′-deoxyribosyltransferases (NDTs), we found a good candidate in an enzyme encoded by Chroococcidiopsis thermalis PCC 7203 (CtNDT). Biophysical and biochemical characterization revealed CtNDT as a homotetramer endowed with good activity and stability at both high temperatures (50–100 °C) and a wide range of pH values (from 3 to 7). CtNDT recognizes purine bases and their corresponding 2′-deoxynucleosides but is also proficient using cytosine and 2′-deoxycytidine as substrates. These unusual features preclude the strict classification of CtNDT as either a type I or a type II NDT and further suggest that this simple subdivision may need to be updated in the future. Our findings also hint at a possible link between oligomeric state and NDT’s substrate specificity. Interestingly from a practical perspective, CtNDT displays high activity (80–100%) in the presence of several water-miscible co-solvents in a proportion of up to 20% and was successfully employed in the enzymatic production of several therapeutic nucleosides such as didanosine, vidarabine, and cytarabine.