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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Acknowledgements
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).
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Fu, X., Albermann, C., Jiang, J. et al. Antibiotic optimization via in vitro glycorandomization. Nat Biotechnol 21, 1467–1469 (2003). https://doi.org/10.1038/nbt909
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DOI: https://doi.org/10.1038/nbt909
