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首页> 外文期刊>Journal of Biotechnology >Immobilized enzymes to convert N-sulfo, N-acetyl heparosan to a critical intermediate in the production of bioengineered heparin
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Immobilized enzymes to convert N-sulfo, N-acetyl heparosan to a critical intermediate in the production of bioengineered heparin

机译：固定化酶将N-磺基，N-乙酰肝素转化为生物工程肝素生产中的关键中间体

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摘要

Heparin is a critically important anticoagulant drug that is prepared from pig intestine. In 2007-2008, there was a crisis in the heparin market when the raw material was adulterated with the toxic polysaccharide, oversulfated chondroitin sulfate, which was associated with 100 deaths in the U.S. alone. As the result of this crisis, our laboratory and others have been actively pursuing alternative sources for this critical drug, including synthetic heparins and bioengineered heparin. In assessing the bioengineering processing costs it has become clear that the use of both enzyme-catalyzed cofactor recycling and enzyme immobilization will be needed for commercialization. In the current study, we examine the use of immobilization of C-5-epimerase and 2-O-sulfotransferase involved in the first enzymatic step in the bioengineered heparin process, as well as arylsulfotransferase-IV involved in cofactor recycling in all three enzymatic steps. We report the successful immobilization of all three enzymes and their use in converting N-sulfo, N-acetyl heparosan into N-sulfo, N-acetyl 2-O-sulfo heparin
机译：肝素是从猪肠中制备的至关重要的抗凝药。在2007年至2008年期间，肝素市场出现了危机，当时原料中掺入了有毒多糖，过硫酸化软骨素硫酸盐，仅在美国就造成100人死亡。由于这场危机，我们的实验室和其他实验室一直在积极寻求这种关键药物的替代来源，包括合成肝素和生物工程肝素。在评估生物工程处理成本时，很明显，将酶催化的辅因子回收和酶固定化用于商业化将是必需的。在当前的研究中，我们研究了在生物工程肝素工艺的第一个酶促步骤中涉及的C-5-表异构酶和2-O-磺基转移酶的固定化，以及在所有三个酶促步骤中参与辅因子回收的芳基磺基转移酶-IV的使用。 。我们报道了所有三种酶的成功固定化及其在将N-磺基，N-乙酰肝素转化为N-磺基，N-乙酰基2-O-磺基肝素中的用途

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