General Principles for Yield Optimization of Nucleoside Phosphorylase-Catalyzed Transglycosylations |
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Authors: | Felix Kaspar Robert T. Giessmann Katja F. Hellendahl Dr. Peter Neubauer Dr. Anke Wagner Dr. Matthias Gimpel |
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Affiliation: | 1. BioNukleo GmbH, Ackerstrasse 76, 13355 Berlin, Germany;2. Department of Biotechnology, Technical University of Berlin, ACK24, Ackerstrasse 76, 13355 Berlin, Germany |
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Abstract: | The biocatalytic synthesis of natural and modified nucleosides with nucleoside phosphorylases offers the protecting-group-free direct glycosylation of free nucleobases in transglycosylation reactions. This contribution presents guiding principles for nucleoside phosphorylase-mediated transglycosylations alongside mathematical tools for straightforward yield optimization. We illustrate how product yields in these reactions can easily be estimated and optimized using the equilibrium constants of phosphorolysis of the nucleosides involved. Furthermore, the varying negative effects of phosphate on transglycosylation yields are demonstrated theoretically and experimentally with several examples. Practical considerations for these reactions from a synthetic perspective are presented, as well as freely available tools that serve to facilitate a reliable choice of reaction conditions to achieve maximum product yields in nucleoside transglycosylation reactions. |
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Keywords: | equilibrium constant nucleosides nucleoside phosphorylases pentose-1-phosphate phosphates |
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