Pathways for the Biosynthesis of NDP Sugars 7 Youai Hao and Joseph S. Lam 7.1 Introduction Bacterial lipopolysaccharide (LPS) is an important surface structure of Gram- negative bacteria for maintaining the integrity of the outer membrane. It is also a virulence factor in many bacteria, particularly those that are pathogens of plants and animals. Structurally, the LPS can be divided into three domains, lipid A, core oligosaccharide and O-polysaccharide (or O-antigen). Its polysaccharide con- stituents contain a great variety of sugars including neutral sugars, charged sugars that are acidic or amino substituted (see Chap. 3). Substitutions and enzy- matic modifications of the basic sugar structure also lead to interesting deoxy or dideoxy sugars. To date, more than 100 new sugar moieties are found in bacterial polysaccharides. In contrast, eukaryotic glycoproteins and glycolipids are synthesized from only nine sugar donors [1, 2]. Since many of the LPS monosaccharide components are rare sugars and only present in certain pathogenic bacteria species, these unusual sugars and the enzymes involved in their synthesis can be targets for novel antimicrobial drug development. An in-depth understanding of the biosyn- thetic pathways of these sugars and the mechanisms of the encoded enzymes is an essential first step to undertake. As demonstrated by Leloir in the 1950s, the sugar units must be converted into sugar nucleotides before they are recognized by specific glycosyltransferases and assembled into a sugar polysaccharide one by one [3]. Different sugars are activated by different nucleotide triphosphate (NTP) to form either nucleotide monophosphate (NMP) or nucleotide diphosphate (NDP) derivatives. Except for Y. Hao • J.S. Lam (*) Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road E., Guelph, Canada, ON, N1G 2W1 e-mail: haoy@uoguelph.ca; jlam@uoguelph.ca Y.A. Knirel and M.A. Valvano (eds.), Bacterial Lipopolysaccharides, DOI 10.1007/978-3-7091-0733-1_7, # Springer-Verlag/Wien 2011 195