Antibiotic optimization via in vitro glycorandomization.
basic_science · Level V
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Abstract
In nature, the attachment of sugars to small molecules is often used to mediate targeting, mechanism of action and/or pharmacology. As an alternative to pathway engineering or total synthesis, we report a useful method, in vitro glycorandomization (IVG), to diversify the glycosylation patterns of complex natural products. We have used flexible glycosyltransferases on nucleotide diphosphosugar (NDP-sugar) libraries to generate glycorandomized natural products and then applied chemoselective ligation to produce monoglycosylated vancomycins that rival vancomycin.
Medical subject headings
- Anti-Bacterial Agents
- Carbohydrates
- Combinatorial Chemistry Techniques
- Glycosyltransferases
- Peptide Library
- Protein Interaction Mapping
- Vancomycin