An Atlas of Human Glycosylation Pathways Enables Display of the Human Glycome by Gene Engineered Cells

Yoshiki Narimatsu; Hiren J. Joshi; Rebecca Nason; Julie Van Coillie; Richard Karlsson; Lingbo Sun; Zilu Ye; Yen-Hsi Chen; Katrine T. Schjoldager; Catharina Steentoft; Sanae Furukawa; Barbara A. Bensing; Paul M. Sullam; Andrew J. Thompson; James C. Paulson; Christian Büll; Gosse J. Adema; Ulla Mandel; Lars Hansen; Eric Paul Bennett; Ajit Varki; Sergey Y. Vakhrushev; Zhang Yang; Henrik Clausen

doi:10.1016/j.molcel.2019.05.017

An Atlas of Human Glycosylation Pathways Enables Display of the Human Glycome by Gene Engineered Cells

Yoshiki Narimatsu^*, Hiren J. Joshi, Rebecca Nason, Julie Van Coillie, Richard Karlsson, Lingbo Sun, Zilu Ye, Yen-Hsi Chen, Katrine T. Schjoldager, Catharina Steentoft, Sanae Furukawa, Barbara A. Bensing, Paul M. Sullam, Andrew J. Thompson, James C. Paulson, Christian Büll, Gosse J. Adema, Ulla Mandel, Lars Hansen, Eric Paul BennettAjit Varki, Sergey Y. Vakhrushev, Zhang Yang, Henrik Clausen

^*Corresponding author for this work

50 Citations (Scopus)

Abstract

The structural diversity of glycans on cells-the glycome-is vast and complex to decipher. Glycan arrays display oligosaccharides and are used to report glycan hapten binding epitopes. Glycan arrays are limited resources and present saccharides without the context of other glycans and glycoconjugates. We used maps of glycosylation pathways to generate a library of isogenic HEK293 cells with combinatorially engineered glycosylation capacities designed to display and dissect the genetic, biosynthetic, and structural basis for glycan binding in a natural context. The cell-based glycan array is self-renewable and reports glycosyltransferase genes required (or blocking) for interactions through logical sequential biosynthetic steps, which is predictive of structural glycan features involved and provides instructions for synthesis, recombinant production, and genetic dissection strategies. Broad utility of the cell-based glycan array is demonstrated, and we uncover higher order binding of microbial adhesins to clustered patches of O-glycans organized by their presentation on proteins.

Original language	English
Journal	Molecular Cell
Volume	75
Issue number	2
Pages (from-to)	394-407, e1-e5
ISSN	1097-2765
DOIs	https://doi.org/10.1016/j.molcel.2019.05.017
Publication status	Published - 25 Jul 2019

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Narimatsu, Y., Joshi, H. J., Nason, R., Van Coillie, J., Karlsson, R., Sun, L., Ye, Z., Chen, Y.-H., Schjoldager, K. T., Steentoft, C., Furukawa, S., Bensing, B. A., Sullam, P. M., Thompson, A. J., Paulson, J. C., Büll, C., Adema, G. J., Mandel, U., Hansen, L., ... Clausen, H. (2019). An Atlas of Human Glycosylation Pathways Enables Display of the Human Glycome by Gene Engineered Cells. Molecular Cell, 75(2), 394-407, e1-e5. https://doi.org/10.1016/j.molcel.2019.05.017

Narimatsu, Y , Joshi, HJ , Nason, R , Van Coillie, J, Karlsson, R, Sun, L, Ye, Z , Chen, Y-H , Schjoldager, KT, Steentoft, C, Furukawa, S, Bensing, BA, Sullam, PM, Thompson, AJ, Paulson, JC, Büll, C, Adema, GJ, Mandel, U , Hansen, L , Bennett, EP, Varki, A, Vakhrushev, SY , Yang, Z & Clausen, H 2019, 'An Atlas of Human Glycosylation Pathways Enables Display of the Human Glycome by Gene Engineered Cells', Molecular Cell, vol. 75, no. 2, pp. 394-407, e1-e5. https://doi.org/10.1016/j.molcel.2019.05.017

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title = "An Atlas of Human Glycosylation Pathways Enables Display of the Human Glycome by Gene Engineered Cells",

abstract = "The structural diversity of glycans on cells-the glycome-is vast and complex to decipher. Glycan arrays display oligosaccharides and are used to report glycan hapten binding epitopes. Glycan arrays are limited resources and present saccharides without the context of other glycans and glycoconjugates. We used maps of glycosylation pathways to generate a library of isogenic HEK293 cells with combinatorially engineered glycosylation capacities designed to display and dissect the genetic, biosynthetic, and structural basis for glycan binding in a natural context. The cell-based glycan array is self-renewable and reports glycosyltransferase genes required (or blocking) for interactions through logical sequential biosynthetic steps, which is predictive of structural glycan features involved and provides instructions for synthesis, recombinant production, and genetic dissection strategies. Broad utility of the cell-based glycan array is demonstrated, and we uncover higher order binding of microbial adhesins to clustered patches of O-glycans organized by their presentation on proteins.",

author = "Yoshiki Narimatsu and Joshi, {Hiren J.} and Rebecca Nason and {Van Coillie}, Julie and Richard Karlsson and Lingbo Sun and Zilu Ye and Yen-Hsi Chen and Schjoldager, {Katrine T.} and Catharina Steentoft and Sanae Furukawa and Bensing, {Barbara A.} and Sullam, {Paul M.} and Thompson, {Andrew J.} and Paulson, {James C.} and Christian B{\"u}ll and Adema, {Gosse J.} and Ulla Mandel and Lars Hansen and Bennett, {Eric Paul} and Ajit Varki and Vakhrushev, {Sergey Y.} and Zhang Yang and Henrik Clausen",

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AU - Narimatsu, Yoshiki

AU - Joshi, Hiren J.

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AU - Van Coillie, Julie

AU - Karlsson, Richard

AU - Sun, Lingbo

AU - Ye, Zilu

AU - Chen, Yen-Hsi

AU - Schjoldager, Katrine T.

AU - Steentoft, Catharina

AU - Furukawa, Sanae

AU - Bensing, Barbara A.

AU - Sullam, Paul M.

AU - Thompson, Andrew J.

AU - Paulson, James C.

AU - Büll, Christian

AU - Adema, Gosse J.

AU - Mandel, Ulla

AU - Hansen, Lars

AU - Bennett, Eric Paul

AU - Varki, Ajit

AU - Vakhrushev, Sergey Y.

AU - Yang, Zhang

AU - Clausen, Henrik

PY - 2019/7/25

Y1 - 2019/7/25

N2 - The structural diversity of glycans on cells-the glycome-is vast and complex to decipher. Glycan arrays display oligosaccharides and are used to report glycan hapten binding epitopes. Glycan arrays are limited resources and present saccharides without the context of other glycans and glycoconjugates. We used maps of glycosylation pathways to generate a library of isogenic HEK293 cells with combinatorially engineered glycosylation capacities designed to display and dissect the genetic, biosynthetic, and structural basis for glycan binding in a natural context. The cell-based glycan array is self-renewable and reports glycosyltransferase genes required (or blocking) for interactions through logical sequential biosynthetic steps, which is predictive of structural glycan features involved and provides instructions for synthesis, recombinant production, and genetic dissection strategies. Broad utility of the cell-based glycan array is demonstrated, and we uncover higher order binding of microbial adhesins to clustered patches of O-glycans organized by their presentation on proteins.

AB - The structural diversity of glycans on cells-the glycome-is vast and complex to decipher. Glycan arrays display oligosaccharides and are used to report glycan hapten binding epitopes. Glycan arrays are limited resources and present saccharides without the context of other glycans and glycoconjugates. We used maps of glycosylation pathways to generate a library of isogenic HEK293 cells with combinatorially engineered glycosylation capacities designed to display and dissect the genetic, biosynthetic, and structural basis for glycan binding in a natural context. The cell-based glycan array is self-renewable and reports glycosyltransferase genes required (or blocking) for interactions through logical sequential biosynthetic steps, which is predictive of structural glycan features involved and provides instructions for synthesis, recombinant production, and genetic dissection strategies. Broad utility of the cell-based glycan array is demonstrated, and we uncover higher order binding of microbial adhesins to clustered patches of O-glycans organized by their presentation on proteins.

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DO - 10.1016/j.molcel.2019.05.017

M3 - Journal article

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SP - 394-407, e1-e5

JO - Molecular Cell

JF - Molecular Cell

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ER -

An Atlas of Human Glycosylation Pathways Enables Display of the Human Glycome by Gene Engineered Cells

Abstract

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