Cytoplasmic glycoengineering enables biosynthesis of nanoscale glycoprotein assemblies.

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 (2019). Cytoplasmic glycoengineering enables biosynthesis of nanoscale glycoprotein assemblies. Nature communications, 10(1), p. 5403. Springer Nature 10.1038/s41467-019-13283-2

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Bachmann, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Springer Nature

Language:

English

Submitter:

Lee-Anne Brand

Date Deposited:

13 Jan 2020 16:00

Last Modified:

13 Mar 2021 14:34

Publisher DOI:

10.1038/s41467-019-13283-2

PubMed ID:

31776333

BORIS DOI:

10.7892/boris.137017

URI:

https://boris.unibe.ch/id/eprint/137017

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