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Fermenting next generation glycosylated therapeutics
1Department of Chemistry, University of California, Davis, 95616, United States. chen@chem.ucdavis.edu
ACS Chemical Biology
|January 22, 2011
Summary
Mutant glycosyltransferases enable glycorandomization for novel compounds. Engineered E. coli now produce these diverse glycosylated natural products economically in vivo.
Area of Science:
- Biochemistry and Synthetic Biology
- Natural Product Drug Discovery
Background:
- Glycosylated natural products possess significant therapeutic potential.
- In vitro glycorandomization using mutant enzymes is key to discovering novel derivatives.
- Economical in vivo production of these compounds remains a challenge.
Purpose of the Study:
- To develop an efficient in vivo method for producing diverse glycorandomized compounds.
- To leverage engineered Escherichia coli for the economic biosynthesis of novel glycosylated natural products.
Main Methods:
- Utilizing mutant glycosyltransferases and sugar nucleotide biosynthetic enzymes.
- Engineering Escherichia coli for the expression of these enzyme mutants.
- Implementing fermentation processes for in vivo production.
Main Results:
- Successful generation of diverse glycorandomized compound libraries.
- Demonstration of economical in vivo production of novel glycosylated natural products.
- Establishment of a scalable platform for producing complex natural product derivatives.
Conclusions:
- Engineered E. coli provide a cost-effective platform for in vivo glycorandomization.
- This approach expands the accessible chemical space for drug discovery.
- The study enables the sustainable production of valuable glycosylated natural products.
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