Synthesis of the Campylobacter jejuni 81‐176 Strain Capsular Polysaccharide Repeating Unit Reveals the Absolute Configuration of its O‐Methyl Phosphoramidate Motif

Abstract

The O‐methyl phosphoramidate (MeOPN) motif is a non‐stoichiometric modification of capsular polysaccharides (CPS) in ≈70 % of all Campylobacter jejuni strains. Infections by C. jejuni lead to food‐borne illnesses and the CPS they produce are key virulence factors. The MeOPN phosphorus atom in these CPS is stereogenic and is found as a single stereoisomer. However, to date, the absolute stereochemistry at this atom has been undefined. We report the synthesis of the three repeating units found in C. jejuni 81‐176 CPS; one of these possesses a MeOPN group. In the course of these studies we established that the stereochemistry of the phosphorus atom in this MeOPN group is R. These studies represent the first unequivocal proof of stereochemistry of this group in any C. jejuni CPS. The compounds produced are anticipated to be useful tools in investigations targeting the function and biosynthesis of this structurally‐interesting modification, which so far has only been identified in campylobacter.

Revisiting Campylobacter jejuni Virulence and Fitness Factors: Role in Sensing, Adapting, and Competing

“…As expected, homopolymeric tracts allow a rapid on/off switching of the C. jejuni CPS genes resulting in variations in CPS arrangements even in C. jejuni isolates that have identical gene contents. In addition to the phase variation observed in CPS sugar composition, C. jejuni CPS is also modified with ethanolamine, glycerol, and nonstoichiometric MeOPN modifications in approximately 75% of C. jejuni strains (Thota et al, 2018).…”

Biosynthetic Pathways to Nonproteinogenic α-Amino Acids

“…The metabolic fate of 234 in the biosynthesis of MeOPN has also been determined. The reactions catalyzed by Cj1415, Cj1416, and Cj1417 ultimately convert 234 to 3′-phospho-5′-cytidine-diphosphoramidate ( 235 ). , The timing of methylation and phosphoryl transfer reactions to ultimately transfer MeOPN to the CPS remain to be delineated, although synthetic routes have demonstrated that the phosphorus in MeOPN exhibits an R -configuration …”

Natural Products Containing ‘Rare’ Organophosphorus Functional Groups

“…The most unusual of the chemical modifications of the CPS is the incorporation of the unique O -methyl phosphoramidate modification on specific sugar residues (2-acetamido-2-deoxy-β- d -galactofuranose— 17 , d -glycero-α- l -gluco-heptopyranose— 18 ) which so far have only been identified in Campylobacter sp. [43,44,45]. The biosynthetic pathway leading to the formation of the P–N bond in CPS was only recently discovered [46,47,48,49].…”