Expanding the glycoengineering toolbox: the rise of bacterial N-linked protein glycosylation

• Glycosylation is the most prevalent post-translational protein modification.
• N-Linked protein glycosylation pathways in bacteria have led to novel therapeutics, vaccines, and diagnostics.
• Bacteria with recombinant N-linked glycosylation pathways improve our understanding of N-glycosylation.
• Current and future prospects in glycoengineering are discussed.

Glycosylation is the most prevalent post-translational modification found on proteins, occurring in all domains of life. Ever since the discovery of asparagine-linked (N-linked) protein glycosylation pathways in bacteria, major efforts have been made to harness these systems for the creation of novel therapeutics, vaccines, and diagnostics. Recent advances such as the ability to produce designer glycans in bacteria, some containing unnatural sugars, and techniques for evolving glycosylation enzymes have spawned an entirely new discipline known as bacterial glycoengineering. In addition to their biotechnological and therapeutic potential, bacteria equipped with recombinant N-linked glycosylation pathways are improving our understanding of the N-glycosylation process. This review discusses the key role played by microorganisms in glycosciences, particularly in the context of N-linked glycosylation.