Biosynthetic incorporation for visualizing bacterial glycans

Area of Science:

• Carbohydrate Chemistry
• Microbiology
• Chemical Biology

Background:

• Cell-surface glycans are crucial for biological processes but lack selective modification methods.
• Protein modification strategies are advanced, but glycan modification remains challenging due to reactivity and genetic encoding limitations.
• Metabolic engineering allows introducing functional groups into glycans via modified nucleotide-sugars.

Purpose of the Study:

• To develop a method for site-selective labeling of arabinofuranose-containing glycans on mycobacterial cell surfaces.
• To leverage bacterial glycosyltransferases' properties for glycan modification.
• To establish a platform for creating chemoselective labeling agents for bacterial monosaccharides.

Main Methods:

• Utilized lipid-linked building blocks as surrogate substrates for glycosyltransferases.
• Employed "biosynthetic incorporation" with bacterial glycosyltransferases for selective product generation.
• Applied the strategy to label glycans on the surface of mycobacterial cells.

Main Results:

• Successfully implemented biosynthetic incorporation to label arabinofuranose-containing glycans.
• Demonstrated the potential of bacterial glycosyltransferases for glycan modification.
• Established a foundation for developing novel chemoselective labeling agents.

Conclusions:

• Biosynthetic incorporation offers a powerful strategy for site-selective glycan modification.
• This approach overcomes limitations in current glycan labeling techniques.
• The platform can be extended to label other important bacterial monosaccharides, advancing glycobiology research.