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Antibiotic optimization via in vitro glycorandomization.

Xun Fu1, Christoph Albermann, Jiqing Jiang

  • 1Laboratory for Biosynthetic Chemistry, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Ave., Madison, Wisconsin 53705, USA.

Nature Biotechnology
|November 11, 2003
PubMed
Summary
This summary is machine-generated.

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In vitro glycorandomization (IVG) diversifies complex natural products by attaching diverse sugar patterns. This method creates novel monoglycosylated vancomycins with properties comparable to the original drug.

Area of Science:

  • Natural Product Chemistry
  • Glycochemistry
  • Synthetic Biology

Background:

  • Glycosylation is crucial for natural product function, influencing targeting, mechanism, and pharmacology.
  • Traditional methods like pathway engineering and total synthesis are often complex and time-consuming for diversifying glycosylation.

Purpose of the Study:

  • To develop an efficient in vitro method for diversifying the glycosylation patterns of complex natural products.
  • To generate novel glycorandomized natural products as an alternative to existing synthetic strategies.

Main Methods:

  • In vitro glycorandomization (IVG) using flexible glycosyltransferases and nucleotide diphosphosugar (NDP-sugar) libraries.
  • Chemoselective ligation was employed to isolate and purify specific glycosylated compounds.

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Main Results:

  • Successfully generated diverse glycorandomized natural products.
  • Produced novel monoglycosylated vancomycins with comparable efficacy to native vancomycin.

Conclusions:

  • In vitro glycorandomization (IVG) offers a powerful and versatile approach for diversifying natural product glycosylation.
  • This method provides a valuable strategy for generating novel drug candidates, exemplified by the creation of potent monoglycosylated vancomycins.