| Toward a bioengineered heparin: challenges and strategies for metabolic engineering of mammalian cells. | |
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MedLine Citation:
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PMID: 22714556 Owner: NLM Status: PubMed-not-MEDLINE |
Abstract/OtherAbstract:
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Heparin is the most widely used pharmaceutical to control blood coagulation in modern medicine. A health crisis that took place in 2008 led to a demand for production of heparin from non-animal sources. Since Chinese hamster ovary (CHO) cells are capable of producing heparan sulfate (HS), a related polysaccharide naturally, and heparin and HS share the same biosynthetic pathway, we hypothesized that heparin could be produced in CHO cells by metabolic engineering. We developed stable human N-deacetylase/N-sulfotransferase (NDST2) and mouse heparan sulfate 3-O-sulfotransferase 1 (Hs3st1) expressing cell lines based on the expression of endogenous enzymes in the HS/heparin pathways of CHO-S cells. Both activity assay and disaccharide analysis showed that engineered HS attained heparin-like characteristics but not identical to pharmaceutical heparin, suggesting that further balancing the expression of transgenes with the expression levels of endogenous enzymes involved in HS/heparin biosynthesis might be necessary. |
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Authors:
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Jong Youn Baik; Clifford L Wang; Bo Yang; Robert J Linhardt; Susan Sharfstein |
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Publication Detail:
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Type: Comment; Journal Article; Research Support, N.I.H., Extramural Date: 2012-06-20 |
Journal Detail:
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Title: Bioengineered Volume: 3 ISSN: 2165-5987 ISO Abbreviation: Bioengineered Publication Date: 2012 Jul-Aug |
Date Detail:
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Created Date: 2012-10-02 Completed Date: 2013-03-26 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 101581063 Medline TA: Bioengineered Country: Unknown |
Other Details:
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Languages: eng Pagination: 227-31 Citation Subset: - |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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R01GM090127/GM/NIGMS NIH HHS |
| Comments/Corrections | |
Comment On:
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Metab Eng. 2012 Mar;14(2):81-90
[PMID:
22326251
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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