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Main Title: Thermodynamic reaction control of nucleoside phosphorolysis
Author(s): Kaspar, Felix
Giessmann, Robert T.
Neubauer, Peter
Wagner, Anke
Gimpel, Matthias
Type: Article
Abstract: Nucleoside analogs represent a class of important drugs for cancer and antiviral treatments. Nucleoside phosphorylases (NPases) catalyze the phosphorolysis of nucleosides and are widely employed for the synthesis of pentose‐1‐phosphates and nucleoside analogs, which are difficult to access via conventional synthetic methods. However, for the vast majority of nucleosides, it has been observed that either no or incomplete conversion of the starting materials is achieved in NPase‐catalyzed reactions. For some substrates, it has been shown that these reactions are reversible equilibrium reactions that adhere to the law of mass action. In this contribution, we broadly demonstrate that nucleoside phosphorolysis is a thermodynamically controlled endothermic reaction that proceeds to a reaction equilibrium dictated by the substrate‐specific equilibrium constant of phosphorolysis, irrespective of the type or amount of NPase used, as shown by several examples. Furthermore, we explored the temperature‐dependency of nucleoside phosphorolysis equilibrium states and provide the apparent transformed reaction enthalpy and apparent transformed reaction entropy for 24 nucleosides, confirming that these conversions are thermodynamically controlled endothermic reactions. This data allows calculation of the Gibbs free energy and, consequently, the equilibrium constant of phosphorolysis at any given reaction temperature. Overall, our investigations revealed that pyrimidine nucleosides are generally more susceptible to phosphorolysis than purine nucleosides. The data disclosed in this work allow the accurate prediction of phosphorolysis or transglycosylation yields for a range of pyrimidine and purine nucleosides and thus serve to empower further research in the field of nucleoside biocatalysis.
Subject(s): nucleosides
nucleoside phosphorylase
nucleoside phosphorolysis
equilibrium constant
Issue Date: 7-Jan-2020
Date Available: 26-Feb-2020
Is Part Of: 10.14279/depositonce-10629
Language Code: en
DDC Class: 540 Chemie und zugeordnete Wissenschaften
660 Chemische Verfahrenstechnik
Sponsor/Funder: DFG, 390540038, EXC 2008: UniSysCat
TU Berlin, Open-Access-Mittel - 2019
Journal Title: Advanced Synthesis & Catalysis
Publisher: Wiley
Volume: 362
Issue: 4
Publisher DOI: 10.1002/adsc.201901230
Page Start: 867
Page End: 876
EISSN: 1615-4169
ISSN: 1615-4150
TU Affiliation(s): Fak. 3 Prozesswissenschaften » Inst. Biotechnologie » FG Bioverfahrenstechnik
Appears in Collections:Technische Universität Berlin » Publications

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