Bacteria Engineered to Glycosylate Full-Length IgG: A Breakthrough in Antibody Production

Scientists have unlocked a powerful new tool in the world of antibody engineering: a bacterial enzyme capable of glycosylating full-length immunoglobulin G (IgG) antibodies.

Glycosylation – the process of attaching sugar molecules to proteins – is a critical modification that shapes the function and efficacy of therapeutic antibodies. Until now, producing authentically glycosylated IgGs required complex and expensive eukaryotic cell systems, such as Chinese hamster ovary (CHO) cells. Attempts to rewire bacteria like Escherichia coli for this task met limited success due to enzyme inefficiencies.

A research team led by Cornell University and collaborators has now reported the discovery of a single-subunit oligosaccharyltransferase (OST) from Desulfovibrio marinus that overcomes these hurdles. Unlike previous bacterial enzymes, this OST shows relaxed substrate specificity, enabling it to glycosylate the conserved Fc domain of IgG antibodies – the very region responsible for triggering immune responses such as antibody-dependent cellular cytotoxicity (ADCC).

When paired with chemoenzymatic remodeling, the glycosylated antibodies displayed human-like glycan structures and bound effectively to FcγRIIIa/CD16a, a receptor critical for therapeutic activity. This marks the first time E. coli has been able to produce IgGs with relevant human glycosylation patterns at meaningful efficiency.

Why It Matters

This breakthrough could transform the biopharmaceutical industry:

Cost reduction: Bacterial systems are faster and cheaper to grow than mammalian cell cultures.
Scalability: Engineered E. coli may offer industrial-scale production of therapeutic antibodies.
Customization: Glycan structures could be fine-tuned to modulate antibody activity, improving therapies for cancer, autoimmune, and infectious diseases.

The discovery not only deepens scientific understanding of bacterial glycosylation but also opens the door to next-generation antibody drugs manufactured in microbes.

As antibody-based therapeutics continue to dominate modern medicine, this microbial innovation could redefine how we design and produce life-saving biologics.

Reference

Sotomayor, B., Donahue, T. C., Mahajan, S. P., Taw, M. N., Hulbert, S. W., Bidstrup, E. J., … & DeLisa, M. P. (2025). Discovery of a single-subunit oligosaccharyltransferase that enables glycosylation of full-length IgG antibodies in bacteria. Nature Communications, 16(1), 6152. https://doi.org/10.1038/s41467-025-61440-7