Deoxysugars in bioactive natural products: development of novel derivatives by altering the sugar pattern

Bioactive natural products are frequently glycosylated with saccharide chains of variable length. These sugars are important for the biological activity of the compounds and they contribute to the interaction with the biological target. The increasing knowledge of sugar biosynthesis pathways and the isolation of a large number of sugar gene clusters from antibiotic-producing actinomycetes are providing tools for combinatorial biosynthesis approaches that can generate potentially improved derivatives with altered sugars in their architecture. Novel derivatives of known bioactive natural products can be produced either in the producer organisms or in heterologous hosts by using different combinatorial biosynthesis strategies. In this article, recent advances in the field are discussed, illustrating the alternative approaches of gene inactivation, gene expression, combining gene inactivation and gene expression, co-expression of genes from different pathways or the use of sugar cassette plasmids to endow a host with the capability of synthesizing new sugars.