Chapter 11: Natural Product Oligosaccharides and Glycosides

Almost every major class of natural product can be found in glycosylated form: from the strictosidine intermediate, plant cyanogenic glycosides, the NRP glycopeptide antibiotics, including vancomycin and bleomycin, as well as the protein kinase ligand rebeccamycin, polyketides erythromycin and ivermectin, plant phytoalexins, such as medicarpin glycosides, and to plant hormone glycoside storage forms of auxin and abscisic acid. There are thousands of glycosyltransferases contained in protein databases. There are also many oligosaccharide natural product variants: from the trisaccharide aminoglycoside antibiotics, the lipo-pentasaccharide moenomycin, to the oligosaccharides in the saccharomicin group. The tailoring of primary hexoses (glucose, mannose, galactose) to selected deoxy- and aminodeoxyhexoses occurs at the level of NDP-sugars by a small cadre of tailoring enzymes that largely work via accessible carbanion chemistry of NDP-4-keto-6-deoxyglucose metabolic intermediates. The altered hydrophobic/hydrophilic balance of the product hexoses suggests important contributions to the bioactivity of the glycine portion of the metabolic end products. This is clearly the case for the cationic aminosugars in aminoglycoside, which direct binding to the bacterial ribosomal anionic RNA as targets.