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

  • Biotechnological Products and Process Engineering
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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.

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Acknowledgments

The authors are grateful for funding from the NIH in the form of grant # HL096972 and the support of the Bioengineered Heparin Consortium for supporting this research.

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Authors and Affiliations

  1. Department of Biology, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA

    Zhenyu Wang, Jonathan S. Dordick & Robert J. Linhardt

  2. Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA

    Bo Yang, Zhenqing Zhang, Mellisa Ly & Robert J. Linhardt

  3. Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA

    Jonathan S. Dordick & Robert J. Linhardt

  4. Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA

    Jonathan S. Dordick & Robert J. Linhardt

  5. The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, 12208, USA

    Majde Takieddin & Shaker Mousa

  6. Division of Medicinal Chemistry and Natural Products, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA

    Jian Liu

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  1. Zhenyu Wang
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  2. Bo Yang
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  8. Jonathan S. Dordick
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  9. Robert J. Linhardt
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Correspondence to Robert J. Linhardt.

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Wang, Z., Yang, B., Zhang, Z. et al. Control of the heparosan N-deacetylation leads to an improved bioengineered heparin. Appl Microbiol Biotechnol 91, 91–99 (2011). https://doi.org/10.1007/s00253-011-3231-5

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  • DOI: https://doi.org/10.1007/s00253-011-3231-5

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