Applied Microbiology and Biotechnology

, Volume 91, Issue 1, pp 91–99 | Cite as

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

  • Zhenyu Wang
  • Bo Yang
  • Zhenqing Zhang
  • Mellisa Ly
  • Majde Takieddin
  • Shaker Mousa
  • Jian Liu
  • Jonathan S. Dordick
  • Robert J. Linhardt
Biotechnological Products and Process Engineering

Abstract

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.

Keywords

Heparin Heparosan Porcine intestine Deacetylation 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Zhenyu Wang
    • 1
  • Bo Yang
    • 2
  • Zhenqing Zhang
    • 2
  • Mellisa Ly
    • 2
  • Majde Takieddin
    • 5
  • Shaker Mousa
    • 5
  • Jian Liu
    • 6
  • Jonathan S. Dordick
    • 1
    • 3
    • 4
  • Robert J. Linhardt
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of BiologyRensselaer Polytechnic InstituteTroyUSA
  2. 2.Department of Chemistry and Chemical BiologyRensselaer Polytechnic InstituteTroyUSA
  3. 3.Department of Chemical and Biological EngineeringRensselaer Polytechnic InstituteTroyUSA
  4. 4.Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary StudiesRensselaer Polytechnic InstituteTroyUSA
  5. 5.The Pharmaceutical Research InstituteAlbany College of Pharmacy and Health SciencesAlbanyUSA
  6. 6.Division of Medicinal Chemistry and Natural Products, Eshelman School of PharmacyUniversity of North CarolinaChapel HillUSA

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