Glycosyltransferases, important tools for drug design.
An increasing appreciation of carbohydrates as components of natural products has uncovered new opportunities in carbohydrate-based drug design. Glycosylated natural products produced by microorganisms contain a variety of different sugars. Usually the biosynthetic pathways to deoxysugars start from a monosacchride-1-phosphate which is converted to a NDP-hexose by a nucleotidyltransferase. Modification of this intermediate by different enzymes (e.g. dehydratases, epimerases, aminotransferases) yields the final sugar. In contrast to microorganisms, plant products mostly contain glucose, galactose, rhamnose and xylose as structural elements. In all organisms the nucleotide-activated sugar is attached to an aglycon by a glycosyltransferrase (GT). As no single universal GT has been uncovered yet, accomplishing the generation of novel glycosylated compounds requires a deep understanding of the function of glycosyltransferases (GTs) and its specificity. In this review we will present important drugs that contain sugar components. We will give an overview about the existing natural product GTs and we will discuss the structural features of GTs. Through specific examples within different compound classes, we will highlight recent examples of metabolic and combinatorial engineering approaches successfully applied to the production of novel glycosylated compounds.
Luzhetskyy
Andriy
A
Institut für Pharmazeutische Wissenschaften, Lehrstuhl für Pharmazeutische Biologie und Biotechnologie Albert-Ludwigs-Universität Freiburg, Stefan-Meier-Strasse 19, 79104 Freiburg, Germany.
Méndez
Carmen
C
Salas
Jose A
JA
Bechthold
Andreas
A
D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry; D001688:Biological Products / Q000096:biosynthesis / Q000737:chemistry; D002384:Catalysis; D015195:Drug Design; D016695:Glycosyltransferases / Q000378:metabolism*; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001688:Biological Products; D018942:Macrolides; D016695:Glycosyltransferases