N-acetylneuraminic acid synthase (NANS), also known as sialic acid (phosphate) synthase (SAS), is a crucial enzyme in the biosynthesis of sialic acids. Sialic acids are a family of nine-carbon sugars that play significant roles in various biological processes, including cell-cell interaction, microbial infection, and immune response .
The human gene NANS encodes the enzyme N-acetylneuraminic acid 9-phosphate synthase (Neu5Ac-9-P synthase). This cytosolic protein is approximately 40 kDa in size and comprises 359 amino acids . The enzyme is involved in the primary synthesis of the most common sialic acid, N-acetylneuraminic acid (Neu5Ac), through a three-enzyme pathway .
NANS catalyzes the condensation of N-acetylmannosamine 6-phosphate (ManNAc-6-P) and phosphoenolpyruvate (PEP) to generate N-acetylneuraminic acid 9-phosphate (Neu5Ac-9-P) . This reaction is a critical step in the biosynthesis of sialic acids, which are essential for the sialylation of glycans . Sialylation is a process that influences various biological functions, including the stability and clearance rate of glycoproteins .
Sialic acids are involved in numerous biological processes. For example, they play a role in the development of neural tissues during embryogenesis and are associated with the appearance and disappearance of polysialic polymers . Additionally, changes in sialic acid content, types, and linkages have been linked to tumorigenesis and cancer metastasis .
Recombinant human NANS protein is expressed in Escherichia coli and is available for various applications, including SDS-PAGE and mass spectrometry (MS) . The recombinant protein is typically purified to >95% purity and is biologically active . It can produce N-acetylneuraminic acid (Neu5Ac) and 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN) using N-acetylmannosamine 6-phosphate and mannose 6-phosphate as substrates .