Amide N-glycosylation by Asm25, an N-glycosyltransferase of ansamitocins

Chemistry & Biology
Peiji ZhaoHeinz G Floss

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 beta-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.

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Citations

Jul 20, 2011·Journal of the American Chemical Society·Shumpei AsamizuTaifo Mahmud
Feb 4, 2010·Journal of the American Chemical Society·Christopher T Walsh, Michael A Fischbach
Jun 30, 2009·Phytochemistry·Annette ErbAndreas Bechthold
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Jul 31, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Fabienne GutackerAndreas Bechthold
Jan 13, 2012·Chembiochem : a European Journal of Chemical Biology·Tobias KnoblochAndreas Kirschning

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