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Updated: Aug 8, 2026

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Hierarchical and Programmable One-Pot Oligosaccharide Synthesis
Published on: September 6, 2019
Enzymatic tools for engineering natural product glycosylation
Sophie Blanchard1, Jon S Thorson
1Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705, USA.
Current Opinion in Chemical Biology
|May 6, 2006
Summary
Combinatorial biosynthesis engineers microbial pathways to create novel glycosylated natural products. This review highlights advances in sugar pathway elucidation and glycosyltransferase development for drug discovery.
Area of Science:
- Natural Product Chemistry
- Biotechnology
- Synthetic Biology
Background:
- Glycosylated natural products are crucial scaffolds for drug development.
- Diversifying glycosylation patterns is key to discovering new therapeutics.
- Chemical and enzymatic methods are used to modify natural product glycosylation.
Purpose of the Study:
- To review recent advancements in combinatorial biosynthesis for generating novel glycosylated natural products.
- To emphasize the importance of understanding nucleotide-sugar biosynthetic pathways.
- To highlight progress in the development and application of glycosyltransferases.
Main Methods:
- In vivo pathway engineering (combinatorial biosynthesis) by co-expressing gene cassettes and glycosyltransferases in host organisms.
- Elucidation of nucleotide-sugar biosynthetic pathways.
- Characterization and engineering of glycosyltransferases.
Main Results:
- Combinatorial biosynthesis enables the generation of diverse glycosylated natural products.
- Advances in pathway engineering have expanded the toolkit for glycosylation diversification.
- Improved understanding of glycosyltransferases facilitates targeted drug design.
Conclusions:
- Combinatorial biosynthesis is a powerful strategy for discovering novel glycosylated natural products with therapeutic potential.
- Continued research into sugar biosynthesis and glycosyltransferases will drive innovation in drug discovery.
- This approach offers a sustainable route to complex carbohydrate-containing pharmaceuticals.
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Oligosaccharide Assembly
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
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Protein Glycosylation
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
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