Amide N-Glycosylation by Asm25, an N-Glycosyltransferase of Ansamitocins

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Abstract

Ansamitocins are potent antitumor maytansinoids produced by Actinosynnema pretiosum. Their biosynthesis involves the initial assembly of a macrolactam polyketide, followed by a series of postpolyketide synthase (PKS) modifications. Three ansamitocin glycosides were isolated from A. pretiosum and fully characterized structurally as novel ansamitocin derivatives, carrying a β-D-glucosyl group attached to the macrolactam amide nitrogen in place of the N-methyl group. By gene inactivation and complementation, asm25 was identified as the N-glycosyltransferase gene responsible for the macrolactam amide N-glycosylation of ansamitocins. Soluble, enzymatically active Asm25 protein was obtained from asm25-expressing E. coli by solubilization from inclusion bodies. Its optimal reaction conditions, including temperature, pH, metal ion requirement, and Km/Kcat, were determined. Asm25 also showed broad substrate specificity toward other ansamycins and synthetic indolin-2-ones. To the best of our knowledge, this represents the first in vitro characterization of a purified antibiotic N-glycosyltransferase. © 2008 Elsevier Ltd. All rights reserved.

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Zhao, P., Bai, L., Ma, J., Zeng, Y., Li, L., Zhang, Y., … Floss, H. G. (2008). Amide N-Glycosylation by Asm25, an N-Glycosyltransferase of Ansamitocins. Chemistry and Biology, 15(8), 863–874. https://doi.org/10.1016/j.chembiol.2008.06.007

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