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; Linhardt, Robert

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.

BIOENGINEERING; HEPARIN; ANTICOAGULANTS; GLYCOSAMINOGLYCANS; SULFONATION

Applied Microbiology & Biotechnology, 2011, Vol 91, Issue 1, p91

0175-7598

Academic Journal

10.1007/s00253-011-3231-5