Immobilized enzymes to convert N-sulfo, N-acetyl heparosan to a critical intermediate in the production of bioengineered heparin

Jian Xiong, Ujjwal Bhaskar, Guoyun Li, Li Fu, Lingyun Li, Fuming Zhang, Jonathan S. Dordick, Robert J. Linhardt

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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 C5-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.

Original languageEnglish
Pages (from-to)241-247
Number of pages7
JournalJournal of Biotechnology
Volume167
Issue number3
DOIs
StatePublished - 10 Sep 2013
Externally publishedYes

Keywords

  • 2-O-sulfotransferase
  • Aryl sulfotransferase IV
  • Heparosan
  • Immobilized enzymes

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