The role of sialic acid synthases in sialic acid biosynthesis

Introduction The sialic acids comprise a diverse family of nine-carbon keto-sugars, the majority of which are structural derivatives of neuraminic acid (Fig. 1). Neuraminic acid has an amino moiety at the C-5 position, and carboxylate at C-2 which confers negative charge at physiological pH. Whereas unsubstituted neuraminic acid is not known to exist in nature, over 40 substituted variations (classified as sialic acids) have now been described.1 Common modifications to the core neuraminic acid framework include O-acetylation and esterification of the hydroxyl moieties, namely at positions C-7, C-8 and C-9 (Fig. 1).2 Multiple substitutions at these positions allow further diversification of sialic acid structure. Other modifications include glycolation (N-glycolylneuraminic acid) and deamination (2-keto-3-deoxy-D-glycero-D-galacto-nononic acid) of the C-5 amino group. N-acetylneuraminic acid (NeuNAc), N-acetylated at position C-5, is the most prevalent sialic acid in nature and is often synonymous with the term sialic acid.1