Antibiotic optimization via in vitro glycorandomization

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

doi:10.1038/nbt909

Antibiotic optimization via in vitro glycorandomization

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

Research output: Contribution to journal › Article › peer-review

209 Citations (SciVal)

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 language	English
Pages (from-to)	1467-1469
Number of pages	3
Journal	Nature Biotechnology
Volume	21
Issue number	12
DOIs	https://doi.org/10.1038/nbt909
State	Published - 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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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.",

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AU - Fu, Xun

AU - Albermann, Christoph

AU - Jiang, Jiqing

AU - Liao, Jianchun

AU - Zhang, Changsheng

AU - Thorson, Jon S.

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Antibiotic optimization via in vitro glycorandomization

Abstract

Bibliographical note

ASJC Scopus subject areas

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