Antibiotic optimization via in vitro glycorandomization.
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.
Fu
Xun
X
Laboratory for Biosynthetic Chemistry, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Ave., Madison, Wisconsin 53705, USA.
Albermann
Christoph
C
Jiang
Jiqing
J
Liao
Jianchun
J
Zhang
Changsheng
C
Thorson
Jon S
JS
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000276:immunology*; D002241:Carbohydrates / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D006031:Glycosylation; D016695:Glycosyltransferases / Q000737:chemistry*; D019151:Peptide Library; D025941:Protein Interaction Mapping / Q000379:methods*; D011786:Quality Control; D014640:Vancomycin / Q000138:chemical synthesis* / Q000276:immunology
D000900:Anti-Bacterial Agents; D002241:Carbohydrates; D019151:Peptide Library; D014640:Vancomycin; D016695:Glycosyltransferases