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Unusual sugar biosynthesis and natural product glycodiversification

Nature volume 446, pages 1008–1016 (2007)Cite this article

Abstract

The enzymes involved in the biosynthesis of carbohydrates and the attachment of sugar units to biological acceptor molecules catalyse an array of chemical transformations and coupling reactions. In prokaryotes, both common sugar precursors and their enzymatically modified derivatives often become substituents of biologically active natural products through the action of glycosyltransferases. Recently, researchers have begun to harness the power of these biological catalysts to alter the sugar structures and glycosylation patterns of natural products both in vivo and in vitro. Biochemical and structural studies of sugar biosynthetic enzymes and glycosyltransferases, coupled with advances in bioengineering methodology, have ushered in a new era of drug development.

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Figure 1: Structural diversity of prokaryotic NDP-sugars derived from NDP-4-keto-6-deoxy-α-D-glucose.
Figure 2: Mechanisms of enzymes catalysing sugar deoxygenation reactions.
Figure 3: Examples of sugar biosynthetic enzymes from the short-chain dehydrogenase/reductase enzyme family.
Figure 4: Mechanism of glycosyltransferases.
Figure 5: Overview of bioengineering strategies.
Figure 6: Glycodiversification of natural products.

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Acknowledgements

We thank the National Institutes of Health for their generous support of this work.

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  1. H.-w.L. (h.w.liu@mail.utexas.edu). Author Information Reprints and permissions information is available at http://npg.nature.com/reprints/index.html

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  1. Institute for Cellular and Molecular Biology, 1 University Station A4810, University of Texas at Austin, Austin, 78712, Texas, USA

    Christopher J. Thibodeaux & Hung-wen Liu

  2. Department of Chemistry and Biochemistry, 1 University Station A5300, University of Texas at Austin, Austin, 78712, Texas, USA

    Charles E. Melançon & Hung-wen Liu

  3. Division of Medicinal Chemistry, College of Pharmacy, 1 University Station A1935, University of Texas at Austin, Austin, 78712, Texas, USA

    Hung-wen Liu

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Note added in proof: Lovering et al. recently demonstrated that the glycosyltransferase domain of a bifunctional glycosyltransferase/transpeptidase enzyme involved in peptidoglycan biosynthesis in Staphylococcus aureus adopts a structural fold that is distinct from that of the GT-A and GT-B glycosyltransferase families, making it the first member of a new family of glycosyltransferases to be structurally characterized98.

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Thibodeaux, C., Melançon, C. & Liu, Hw. Unusual sugar biosynthesis and natural product glycodiversification. Nature 446, 1008–1016 (2007). https://doi.org/10.1038/nature05814

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