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glycero-manno-Heptose is widely present in the lipopolysaccharide (LPS) of most Gram-negative bacteria. This carbohydrate and its derivatives are sometimes also found in capsules and O antigens as well as in the glycan moieties of bacterial cell surface (S-layer) glycoproteins. Gram-negative bacteria with a heptoseless LPS are highly sensitive to hydrophobic substances and they also display reduced virulence in animal infection models. Thus heptose biosynthetic genes and their products are potentially attractive targets for developing novel antimicrobial compounds. Recent work in our laboratories has elucidated the complete pathways for biosynthesis of the nucleotide-activated heptosyl precursors (Fig. 1), which are utilized in the assembly of the LPS inner-core oligosaccharide and a bacterial S-layer glycoprotein (Kneidinger et al., 2001, 2002). We review the state of the art of these biosynthesis pathways, particularly regarding the enzyme functions involved in the various steps of the biosynthesis of ADP--glycero--mannoheptose and GDP--glycero--manno-heptose. We also provide a comparative genetic analysis of the biosynthetic genes in sequenced bacterial genomes.

Novel pathways for biosynthesis of nucleotide-activated glycero-manno-heptose precursors of bacterial glycoproteins and cell surface polysaccharides