Biosynthesis of the O‐Antigenic Side‐Chains of Lipopolysaccharide in Salmonella —Its Biochemistry and Genetics

The biosynthesis of O-antigenic lipopolysaccharides (LPS) in salmonella proceeds in two stages (for review see ref. [1]). First, the R core, comprising the central portion of LPS, is synthesized. Then, the O-antigenic side-chains (O side-chains), which have been synthesized on a lipid carrier, are attached to the R core. The O side-chains of group B salmonella such as Salmonella typhimurium consists of repeat units containing D-galactose, D-mannose, L-rhamnose, and abequose (Fig. 1). From smooth wild type, one can isolate rough mutants which synthesize LPS devoid of O side-chains. Stocker and associates have separated rough mutants of S. typhimurium into two main genetic classes, which they called rough A (rouA) and rough B (rouB) [8, 9]. Since it has become clear that rouA and rouB represent gene clusters rather than individual loci, they will hereafter be designated by the symbols rfa and rfb. Stocker's group suggested that the rfa gene cluster, located between str and metA, determines the synthesis of R core, whereas the synthesis of O side-chains is determined by the genes of rfb cluster, located between metG and his [8, 9]. Thus rfa mutants can and do synthesize O side-chains, but cannot attach them to the incomplete core they synthesize. In contrast, rfb mutants generally cannot synthesize O side-chains at all. The biosynthesis of O side-chains can be divided into two stages. In the first stage, component sugars must be synthesized and activated in the form of nucleotide diphosphate sugars. In the second stage, the sugars are "polymerized" to form long polysaccharide chains. We shall discuss these two stages in succession. 1. Synthesis of Nucleoside Diphosphate Sugars. The pathway for the synthesis of nucleotide-sugars containing galactose, abequose, mannose, and rhamnose is shown in Fig. 2. We have shown, through interspecific crosses of salmonella, that the rfb gene