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Campylobacterjejuni is a Gram-negative pathogenicbacterium commonly found in chickens and is the leading cause of humandiarrheal disease worldwide. The various serotypes of C.?jejuni produce structurally distinct capsular polysaccharides （CPSs） onthe exterior surfaces of the cell wall. The capsular polysaccharidefrom C.?jejuni serotype HS:5 is composed ofa repeating sequence of d-glycero-d-manno-heptose and d-glucitol-6-phosphate.We previously defined the pathway for the production of d-glycero-d-manno-heptosein C.?jejuni. Here, we elucidate the biosyntheticpathway for the assembly of cytidine diphosphate （CDP）-6-d-glucitol by the combined action of two previously uncharacterizedenzymes. The first enzyme catalyzes the formation of CDP-6-d-fructose from cytidine triphosphate （CTP） and d-fructose-6-phosphate.The second enzyme reduces CDP-6-d-fructose with NADPH togenerate CDP-6-d-glucitol. Using sequence similarity network（SSN） and genome neighborhood network （GNN） analyses, we predict thatthese pairs of proteins are responsible for the biosynthesis of CDP-6-d-glucitol and/or CDP-d-mannitol in the lipopolysaccharides（LPSs） and capsular polysaccharides in more than 200 other organisms.In addition, high resolution X-ray structures of the second enzymeare reported, which provide novel insight into the manner in whichan open-chain nucleotide-linked sugar is harbored in an active sitecleft.
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