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An automated platform for the enzyme-mediated assembly of complex oligosaccharides


An automated platform that can synthesize a wide range of complex carbohydrates will greatly increase their accessibility and should facilitate progress in glycoscience. Here we report a fully automated process for enzyme-mediated oligosaccharide synthesis that can give easy access to different classes of complex glycans including poly-N-acetyllactosamine derivatives, human milk oligosaccharides, gangliosides and N-glycans. Our automated platform uses a catch and release approach in which glycosyltransferase-catalysed reactions are performed in solution and product purification is accomplished by solid phase extraction. We developed a sulfonate tag that can easily be installed and enables highly efficient solid phase extraction and product release using a single set of washing conditions, regardless of the complexity of the glycan. Using this custom-built synthesizer, as many as 15 reaction cycles can be performed in an automated fashion without a need for lyophilization or buffer exchange steps.

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Fig. 1: Automation of enzyme-mediated oligosaccharide assembly.
Fig. 2: Automated enzymatic synthesis of poly-LacNAc and derivatives thereof.
Fig. 3: Automated synthesis of HMOs and gangliosides.
Fig. 4: Automated synthesis of asymmetrical N-glycan 22 and removal of tag to afford 23.

Data availability

All data related to this study are included in this Article and the Supplementary Information and are also available from the authors upon request.


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This research was supported by the National Institute of General Medical Sciences (P01GM107012 and U01GM120408 to G.-J.B. and K.W.M.), the US National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research benefitted from instrumentation provided by NIH grant S10 RR027097.

Author information




T.L., L.L., K.W.M. and G.-J.B. designed the research. T.L., L.L., N.W., J.-Y.Y. and D.G.C. performed the research. J.-Y.Y. and D.G.C. contributed new reagents. T.L., L.L. and G.-J.B. wrote the paper.

Corresponding author

Correspondence to Geert-Jan Boons.

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The authors declare no competing interests.

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Supplementary information

Supplementary Information

Materials and detailed Methods, Supplementary Figures 1–33, Supplementary Tables 1–21 and copies of NMR spectra.

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Li, T., Liu, L., Wei, N. et al. An automated platform for the enzyme-mediated assembly of complex oligosaccharides. Nature Chem 11, 229–236 (2019).

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