2. Academic Validation
  3. Discovery of a single-subunit oligosaccharyltransferase that enables glycosylation of full-length IgG antibodies in bacteria

Discovery of a single-subunit oligosaccharyltransferase that enables glycosylation of full-length IgG antibodies in bacteria

  • Nat Commun. 2025 Jul 4;16(1):6152. doi: 10.1038/s41467-025-61440-7.
Belen Sotomayor 1,  Thomas C Donahue 1 2,  Sai Pooja Mahajan 3,  May N Taw 4,  Sophia W Hulbert 5,  Erik J Bidstrup 1,  D Natasha Owitipana 2,  Alexandra Pang 1,  Xu Yang 6,  Souvik Ghosal 7,  Christopher A Alabi 1 7,  Parastoo Azadi 6,  Jeffrey J Gray 3,  Michael C Jewett 8,  Lai-Xi Wang 2,  Matthew P DeLisa 9 10 11 12
Affiliations

Affiliations

  • 1 Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, 14853, USA.
  • 2 Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA.
  • 3 Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
  • 4 Department of Microbiology, Cornell University, Ithaca, NY, 14853, USA.
  • 5 Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY, 14853, USA.
  • 6 Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA, 30602-4712, USA.
  • 7 Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA.
  • 8 Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • 9 Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, 14853, USA. md255@cornell.edu.
  • 10 Department of Microbiology, Cornell University, Ithaca, NY, 14853, USA. md255@cornell.edu.
  • 11 Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY, 14853, USA. md255@cornell.edu.
  • 12 Cornell Institute of Biotechnology, Cornell University, 130 Biotechnology Building, Ithaca, NY, 14853, USA. md255@cornell.edu.
PMID: 40610439 DOI: 10.1038/s41467-025-61440-7
Abstract

Human immunoglobulin G (IgG) antibodies are a major class of biotherapeutics and undergo N-linked glycosylation in their Fc domain, which is critical for immune functions and therapeutic activity. Hence, technologies for producing authentically glycosylated IgGs are in high demand. Previous attempts to engineer Escherichia coli for this purpose have met limited success due in part to the lack of oligosaccharyltransferase (OST) Enzymes that can install N-glycans at the conserved N297 site in the Fc region. Here, we identify a single-subunit OST from Desulfovibrio marinus with relaxed substrate specificity that catalyzes glycosylation of native Fc acceptor sites. By chemoenzymatic remodeling the attached Bacterial glycans to homogeneous, asialo complex-type G2 N-glycans, the E. coli-derived Fc binds human FcγRIIIa/CD16a, a key receptor for antibody-dependent cellular cytotoxicity (ADCC). Overall, the discovery of D. marinus OST provides previously unavailable biocatalytic capabilities and sets the stage for using E. coli to produce fully human antibodies.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z