A modular, reusable biocatalytic flow system for UDP-GlcNAc production

We report here the continuous flow synthesis of a high-value sugar nucleotide. Immobilisation of enzymes onto solid carriers permitted transfer of the biocatalysts into packed bed reactors to realise a continuous biocatalytic platform for the synthesis of uridine diphosphate N -acetylglucosamine (UD...

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Bibliographic Details
Published in:Reaction chemistry & engineering Vol. 1; no. 6; pp. 1221 - 1226
Main Authors: Roberts, Tom L, Dolan, Jonathan P, Miller, Gavin J, Lima, Marcelo A. D, Cosgrove, Sebastian C
Format: Journal Article
Language:English
Published: England Royal Society of Chemistry 28.05.2025
The Royal Society of Chemistry
Subjects:
Chemistry
Continuous flow
Glycan
Glycoproteins
Modular systems
Nucleotides
Oligosaccharides
Packed beds
Synthesis
Thermal stability
ISSN:2058-9883, 2058-9883
Online Access:Get full text
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Summary:We report here the continuous flow synthesis of a high-value sugar nucleotide. Immobilisation of enzymes onto solid carriers permitted transfer of the biocatalysts into packed bed reactors to realise a continuous biocatalytic platform for the synthesis of uridine diphosphate N -acetylglucosamine (UDP-GlcNAc) on 100 mg scale, with capacity for multiple reuses. The modular continuous flow approach described here represents a significant, up to 11-fold, improvement in space time yield (STY) when compared to batch studies, along with preventing product induced enzyme inhibition, reducing the need for an additional enzyme to break down inorganic pyrophosphate (PPi). The modular nature of the system has also allowed tailored conditions to be applied to each enzyme, overcoming issues relating to thermal stability. This development presents a platform approach towards a more efficient, continuous synthesis of important glycan targets including glycoproteins, specific oligosaccharide sequences and glycosylated drug targets. Roberts et al. demonstrate UDP- N -acetyl glucosamine can be produced in a continuous biocatalytic system. Improvements versus batch include simplified downstream processing, 11-fold increase in space time yield and improvement in enzyme lifetime.
Bibliography:https://doi.org/10.1039/d5re00127g
Electronic supplementary information (ESI) available. See DOI
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ISSN:2058-9883
2058-9883
DOI:10.1039/d5re00127g