One-Pot Enzymatic Synthesis of Heparin from N-Sulfoheparosan

Methods Mol Biol. 2022:2303:3-11. doi: 10.1007/978-1-0716-1398-6_1.

Abstract

Heparin, a glycosaminoglycan-based anticoagulant drug, is prepared as an extract of animal tissues. Heparosan, an Escherichia coli (E. coli) K5 capsular polysaccharide with the structure →4)-β-D-glucuronic acid (1 → 4)-β-D-N-acetylglucosamine (1→, corresponds to the precursor backbone in the Golgi-based biosynthesis of heparin. Anticoagulant heparin is prepared in a one-pot synthesis using a chemically prepared derivative of heparosan called N-sulfoheparosan (NSH), recombinant Golgi enzymes expressed in E. coli, and the 3-phosphoadenosine-5-phosphosulfate (PAPS) cofactor.

Keywords: 3-Phosphoadenosine-5-phosphosulfate; Biosynthesis; Enzymes; Heparan sulfate; Heparin; Heparosan.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anticoagulants
  • Disaccharides
  • Escherichia coli* / genetics
  • Glycosaminoglycans
  • Heparin / metabolism*
  • Phosphoadenosine Phosphosulfate

Substances

  • Anticoagulants
  • Disaccharides
  • Glycosaminoglycans
  • heparosan
  • Phosphoadenosine Phosphosulfate
  • Heparin