Antibiotic optimization via in vitro glycorandomization

Xun Fu, Christoph Albermann, Jiqing Jiang, Jianchun Liao, Changsheng Zhang, Jon S. Thorson

Research output: Contribution to journalArticlepeer-review

207 Scopus citations

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.

Original languageEnglish
Pages (from-to)1467-1469
Number of pages3
JournalNature Biotechnology
Volume21
Issue number12
DOIs
StatePublished - Dec 2003

Bibliographical note

Funding Information:
We gratefully acknowledge the University of Wisconsin-Madison School of Pharmacy Analytical Facility for LC-MS support (Gary Girdaukas) and Christopher T. Walsh and Heather Losey for graciously providing the glycosyltransferase E expression strain. J.S.T. is an Alfred P. Sloan Research Fellow. This work was supported in part by the US National Institutes of Health (GM58196, CA84374 and AI52218).

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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