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Bacterial CMP-sialic acid synthetases: production, properties, and applications

Abstract

Sialic acids are abundant nine-carbon sugars expressed terminally on glycoconjugates of eukaryotic cells and are crucial for a variety of cell biological functions such as cell–cell adhesion, intracellular signaling, and in regulation of glycoproteins stability. In bacteria, N-acetylneuraminic acid (Neu5Ac) polymers are important virulence factors. Cytidine 5′-monophosphate (CMP)-N-acetylneuraminic acid synthetase (CSS; EC 2.7.7.43), the key enzyme that synthesizes CMP-N-acetylneuraminic acid, the donor molecule for numerous sialyltransferase reactions, is present in both prokaryotes and eukaryotic systems. Herein, we emphasize the source, function, and biotechnological applications of CSS enzymes from bacterial sources. To date, only a few CSS from pathogenic bacterial species such as Neisseria meningitidis, Escherichia coli, group B streptococci, Haemophilus ducreyi, and Pasteurella hemolytica and an enzyme from nonpathogenic bacterium, Clostridium thermocellum, have been described. Overall, the enzymes from both Gram-positive and Gram-negative bacteria share common catalytic properties such as their dependency on divalent cation, temperature and pH profiles, and catalytic mechanisms. The enzymes, however, can be categorized as smaller and larger enzymes depending on their molecular weight. The larger enzymes in some cases are bifunctional; they have exhibited acetylhydrolase activity in addition to their sugar nucleotidyltransferase activity. The CSSs are important enzymes for the chemoenzymatic synthesis of various sialooligosaccharides of significance in biotechnology.

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Acknowledgements

This material is based in part upon work supported by the National Science Foundation under CAREER Grant No. 0349139 and the Herman Frasch Foundation (ACS-PRF).

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Correspondence to Rahman M. Mizanur or Nicola L. Pohl.

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Mizanur, R.M., Pohl, N.L. Bacterial CMP-sialic acid synthetases: production, properties, and applications. Appl Microbiol Biotechnol 80, 757 (2008). https://doi.org/10.1007/s00253-008-1643-7

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Keywords

  • Sialic acid
  • CMP-sialic acid synthetases
  • Sugar nucleotide