Regulation of capsular polysialic acid biosynthesis by N-acetyl-d-mannosamine, an intermediate of sialic acid metabolism

N-Acetyl-d-mannosamine (ManNAc) is a specific substrate for the synthesis of N-acetylneuraminic acid, the essential precursor of bacterial capsular polysialic acid (PA). When Escherichia coli K92 used ManNAc as a carbon source, we observed a dramatic reduction (up to 90%) in in vivo PA production. Experiments in which the carbon source was changed revealed that the maximal inhibitory effect occurred when this sugar was present in the medium before the logarithmic phase of bacterial growth had started. Enzymatic analysis revealed that high concentrations of ManNAc-6-phosphate inhibit NeuAc lyase, the enzyme that synthesizes NeuAc for PA biosynthesis in E. coli. These results indicate that ManNAc-6-phosphate is able to regulate NeuAc lyase activity and modulate the PA synthesis.