Advances in Enzymatic Glycoside Synthesis

Area of Science:

• Carbohydrate Chemistry and Biochemistry
• Enzymology
• Glycobiology

Background:

• A significant gap exists in robust platforms for the facile synthesis of defined glycans.
• Understanding diverse carbohydrate functions, including cell signaling, necessitates controlled synthesis methods.
• Current methods like chemical synthesis are inefficient, and natural enzymes (glycosyltransferases) are difficult to scale.

Purpose of the Study:

• To address the need for controlled glycan synthesis.
• To explore the potential of engineered enzymes (glycosynthases) for glycan assembly.
• To enable the production of glycans for use as research probes, inhibitors, and therapeutics.

Main Methods:

• Utilizing glycoside hydrolases in a transglycosylation mode.
• Engineering glycoside hydrolases into 'glycosynthases' for efficient glycoside assembly.
• Exploring the application of these enzymes in remodelling glycosylation patterns of therapeutic proteins.

Main Results:

• Glycosynthases provide a viable route to synthesize valuable glycans.
• Engineered glycoside hydrolases can overcome limitations of traditional synthesis methods.
• This approach facilitates access to glycans for diverse applications.

Conclusions:

• Engineered glycosynthases offer a powerful tool for controlled glycan synthesis.
• This technology is essential for advancing the study of carbohydrate functions in biology.
• The remodelling of therapeutic protein glycosylation using these enzymes represents a key area for future research and industrial application.