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

Wang, Zhenyu
Yang, Bo
Zhang, Zhenqing
Ly, Mellisa
Takieddin, Majde
Mousa, Shaker
Liu, Jian
Dordick, Jonathan S.
Linhardt, Robert J.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Control of the heparosan N-deacetylation leads to an improved bioengineered heparin, Z. Wang, B. Yang, Z. Zhang, M. Ly, M. Takieddin, S. Mousa, J. Liu, J. S. Dordick, R. J. Linhardt Applied Microbiology and Biotechnology, 91, 91-99, 2011.
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.
Applied Microbiology and Biotechnology, 91, 91-99
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
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Rensselaer Polytechnic Institute, Troy, NY
Applied Microbiology and Biotechnology
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