Cytoplasmic glycoengineering enables biosynthesis of nanoscale glycoprotein assemblies

Glycosylation of proteins profoundly impacts their physical and biological properties. Yet our ability to engineer novel glycoprotein structures remains limited. Established bacterial glycoengineering platforms require secretion of the acceptor protein to the periplasmic space and preassembly of the...

Full description

Saved in:

Bibliographic Details
Published in:	Nature communications Vol. 10; no. 1; pp. 5403 - 10
Main Authors:	Tytgat, Hanne L. P., Lin, Chia-wei, Levasseur, Mikail D., Tomek, Markus B., Rutschmann, Christoph, Mock, Jacqueline, Liebscher, Nora, Terasaka, Naohiro, Azuma, Yusuke, Wetter, Michael, Bachmann, Martin F., Hilvert, Donald, Aebi, Markus, Keys, Timothy G.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 27-11-2019 Nature Publishing Group Nature Portfolio
Subjects:	14/28 45/22 45/23 45/70 631/61/318 631/61/338/552 631/61/350/2093 631/92/221 82/16 82/29 82/58 82/83 Bacteria Benzazepines Biological properties Biomedical materials Biosynthesis Cytoplasm Cytoplasm - metabolism E coli Epitopes Epitopes - metabolism Escherichia coli - genetics Escherichia coli - metabolism Glucose - chemistry Glucose - metabolism Glucosyltransferases - metabolism Glycan Glycoproteins Glycoproteins - biosynthesis Glycoproteins - genetics Glycoproteins - immunology Glycosylation Glycosyltransferase Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism Humanities and Social Sciences Lipids Localization Metabolic Engineering - methods Monosaccharides multidisciplinary Nanomaterials Nanotechnology Oligosaccharides Periplasmic space Polysaccharides Polysaccharides - metabolism Promoter Regions, Genetic Proteins Recombinant Proteins - biosynthesis Recombinant Proteins - genetics Science Science (multidisciplinary) Secretion Substrates
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Glycosylation of proteins profoundly impacts their physical and biological properties. Yet our ability to engineer novel glycoprotein structures remains limited. Established bacterial glycoengineering platforms require secretion of the acceptor protein to the periplasmic space and preassembly of the oligosaccharide substrate as a lipid-linked precursor, limiting access to protein and glycan substrates respectively. Here, we circumvent these bottlenecks by developing a facile glycoengineering platform that operates in the bacterial cytoplasm. The Glycoli platform leverages a recently discovered site-specific polypeptide glycosyltransferase together with variable glycosyltransferase modules to synthesize defined glycans, of bacterial or mammalian origin, directly onto recombinant proteins in the E. coli cytoplasm. We exploit the cytoplasmic localization of this glycoengineering platform to generate a variety of multivalent glycostructures, including self-assembling nanomaterials bearing hundreds of copies of the glycan epitope. This work establishes cytoplasmic glycoengineering as a powerful platform for producing glycoprotein structures with diverse future biomedical applications. Established bacterial glycoengineering platforms limit access to protein and glycan substrates. Here the authors design a cytoplasmic protein glycosylation system, Glycoli, to generate a variety of multivalent glycostructures.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-019-13283-2