Complete set of glycosyltransferase structures in the calicheamicin biosynthetic pathway reveals the origin of regiospecificity

Aram Chang, Shanteri Singh, Kate E. Helmich, Randal D. Goff, Craig A. Bingman, Jon S. Thorson, George N. Phillips

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Glycosyltransferases are useful synthetic catalysts for generating natural products with sugar moieties. Although several natural product glycosyltransferase structures have been reported, design principles of glycosyltransferase engineering for the generation of glycodiversified natural products has fallen short of its promise, partly due to a lack of understanding of the relationship between structure and function. Here, we report structures of all four calicheamicin glycosyltransferases (CalG1, CalG2, CalG3, and CalG4), whose catalytic functions are clearly regiospecific. Comparison of these four structures reveals a conserved sugar donor binding motif and the principles of acceptor binding region reshaping. Among them, CalG2 possesses a unique catalytic motif for glycosylation of hydroxylamine. Multiple glycosyltransferase structures in a single natural product biosynthetic pathway are a valuable resource for understanding regiospecific reactions and substrate selectivities and will help future glycosyltransferase engineering.

Original languageEnglish
Pages (from-to)17649-17654
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number43
DOIs
StatePublished - Oct 25 2011

ASJC Scopus subject areas

  • General

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