Sialic acid is synthesized by glucosamine 6 phosphate and acetyl-CoA through a transferase, resulting in N-acetylglucosamine-6-P. This becomes N-acetylmannosamine-6-P through epimerization, which reacts with phosphoenolpyruvate producing N-acetylneuraminic-9-P (sialic acid). For it to become active to enter in the oligosaccharide biosynthesis process of the cell, a monophosphate nucleoside is added, which comes from a cytidine triphosphate, turning sialic acid into cytidine monophosphate-sialic acid (CMP-sialic acid). This compound is synthesized in the nucleus of the animal cell.
In bacterial systems, sialic acids can be also biosynthesized by an aldolase. This enzyme uses for example a mannose derivative as a substrate, inserting three carbons from pyruvate into the resulting sialic acid structure. These enzymes can be used for chemoenzymatic synthesis of sialic acid derivatives.