Control of the heparosan N-deacetylation leads to an improved bioengineered heparin

Appl Microbiol Biotechnol. 2011 Jul;91(1):91-9. doi: 10.1007/s00253-011-3231-5. Epub 2011 Apr 12.


The production of the anticoagulant drug heparin from non-animal sources has a number of advantages over the current commercial production of heparin. These advantages include better source material availability, improved quality control, and reduced concerns about animal virus or prion impurities. A bioengineered heparin would have to be chemically and biologically equivalent to be substituted for animal-sourced heparin as a pharmaceutical. In an effort to produce bioengineered heparin that more closely resembles pharmaceutical heparin, we have investigated a key step in the process involving the N-deacetylation of heparosan. The extent of N-deacetylation directly affects the N-acetyl/N-sulfo ratio in bioengineered heparin and also impacts its molecular weight. Previous studies have demonstrated that the presence and quantity of N-acetylglucosamine in the nascent glycosaminoglycan chain, serving as the substrate for the subsequent enzymatic modifications (C5 epimerization and O-sulfonation), can impact the action of these enzymes and, thus, the content and distribution of iduronic acid and O-sulfo groups. In this study, we control the N-deacetylation of heparosan to produce a bioengineered heparin with an N-acetyl/N-sulfo ratio and molecular weight that is similar to animal-sourced pharmaceutical heparin. The structural composition and anticoagulant activity of the resultant bioengineered heparin was extensively characterized and compared to pharmaceutical heparin obtained from porcine intestinal mucosa.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism
  • Anticoagulants / chemistry
  • Anticoagulants / metabolism*
  • Anticoagulants / pharmacology
  • Disaccharides / chemistry
  • Disaccharides / metabolism*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Heparin / chemistry
  • Heparin / metabolism*
  • Heparin / pharmacology
  • Humans
  • Industrial Microbiology / methods*
  • Molecular Structure
  • Molecular Weight


  • Anticoagulants
  • Disaccharides
  • heparosan
  • Heparin
  • Acetylglucosamine