Document Detail


Toward a bioengineered heparin: challenges and strategies for metabolic engineering of mammalian cells.
MedLine Citation:
PMID:  22714556     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jong Youn Baik; Clifford L Wang; Bo Yang; Robert J Linhardt; Susan Sharfstein
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Publication Detail:
Type:  Comment; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-06-20
Journal Detail:
Title:  Bioengineered     Volume:  3     ISSN:  2165-5987     ISO Abbreviation:  Bioengineered     Publication Date:    2012 Jul-Aug
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-03-26     Revised Date:  2013-07-19    
Medline Journal Info:
Nlm Unique ID:  101581063     Medline TA:  Bioengineered     Country:  Unknown    
Other Details:
Languages:  eng     Pagination:  227-31     Citation Subset:  -    
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MeSH Terms
Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
R01 GM038060/GM/NIGMS NIH HHS; R01GM090127/GM/NIGMS NIH HHS
Comments/Corrections
Comment On:
Metab Eng. 2012 Mar;14(2):81-90   [PMID:  22326251 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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