Chapter 11. Sugar biosynthesis and modification

Many bioactive compounds contain as part of their molecules one or more deoxysugar units. Their presence in the final compound is generally necessary for biological activity. These sugars derive from common monosaccharides, like d-glucose, which have lost one or more hydroxyl groups (monodeoxysugars, dideoxysugars, trideoxysugars) during their biosynthesis. These deoxysugars are transferred to the final molecule by the action of a glycosyltransferase. Here, we first summarize the different biosynthetic steps required for the generation of the different families of deoxysugars, including those containing extra methyl or amino groups, or tailoring modifications of the glycosylated compounds. We then give examples of several strategies for modification of the glycosylation pattern of a given bioactive compound: inactivation of genes involved in the biosynthesis of deoxysugars; heterologous expression of genes for the biosynthesis or transfer of a specific deoxysugar; and combinatorial biosynthesis (including the use of gene cassette plasmids). Finally, we report techniques for the isolation and detection of the new glycosylated derivatives generated using these strategies.