A prominent attribute of chemical structure in microbial and plant natural products is aromatic C-glycosylation. In plants, various flavonoid natural products have a β-C-d-glucosyl moiety attached to their core structure. Natural product C-glycosides have attracted significant attention for their own unique bioactivity as well as for representing non-hydrolysable analogs of the canonical O-glycosides. The biosynthesis of natural product C-glycosides is accomplished by sugar nucleotide-dependent (Leloir) glycosyltransferases. Here, we provide an overview on the C-glycosyltransferases of microbial, plant and insect origin that have been biochemically characterized. Despite sharing basic evolutionary relationships, as evidenced by their common membership to glycosyltransferase family GT-1 and conserved GT-B structural fold, the known C-glycosyltransferases are diverse in the structural features that govern their reactivity, selectivity and specificity. Bifunctional glycosyltransferases can form C- and O-glycosides dependent on the structure of the aglycon acceptor. Recent crystal structures of plant C-glycosyltransferases and di-C-glycosyltransferases complement earlier structural studies of bacterial enzymes and provide important molecular insight into the enzymatic discrimination between C- and O-glycosylation. Studies of enzyme structure and mechanism converge on the view of a single displacement (SN2)-like mechanism of enzymatic C-glycosyl transfer, largely analogous to O-glycosyl transfer. The distinction between reactions at the O- or C-acceptor atom is achieved through the precise positioning of the acceptor relative to the donor substrate in the binding pocket. Nonetheless, C-glycosyltransferases may differ in the catalytic strategy applied to induce nucleophilic reactivity at the acceptor carbon. Evidence from the mutagenesis of C-glycosyltransferases may become useful in engineering these enzymes for tailored reactivity.
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August 2020
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The transcript is populated with numerous overlapping codes that regulate all steps of gene expression. These codes cannot be readily discovered and understood without the use of computational modelling and algorithms. In this issue (see pages 1519–1528), Bahiri-Elitzur and Tuller summarize and discuss the different approaches that have been employed in the field in recent years. This cover artwork has been created by Hagar Messer and was provided by Tamir Tuller.
Review Article|
July 13 2020
Leloir glycosyltransferases of natural product C-glycosylation: structure, mechanism and specificity
Gregor Tegl;
Gregor Tegl
1Institute of Biotechnology and Biochemical Engineering, Graz University of Technology, NAWI Graz, 8010 Graz, Austria
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Bernd Nidetzky
1Institute of Biotechnology and Biochemical Engineering, Graz University of Technology, NAWI Graz, 8010 Graz, Austria
2Austrian Centre of Industrial Biotechnology (acib), 8010 Graz, Austria
Correspondence: Bernd Nidetzky (bernd.nidetzky@tugraz.at)
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Biochem Soc Trans (2020) 48 (4): 1583–1598.
Article history
Received:
May 01 2020
Revision Received:
June 05 2020
Accepted:
June 10 2020
Citation
Gregor Tegl, Bernd Nidetzky; Leloir glycosyltransferases of natural product C-glycosylation: structure, mechanism and specificity. Biochem Soc Trans 28 August 2020; 48 (4): 1583–1598. doi: https://doi.org/10.1042/BST20191140
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