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dc.rights.licenseCC BY — Creative Commons Attribution
dc.contributor.authorDatta, Payel
dc.contributor.authorLi, Guoyun
dc.contributor.authorYang, Bo
dc.contributor.authorZhao, Xue
dc.contributor.authorBaik, Jong Youn
dc.contributor.authorGemmill, Trent R.
dc.contributor.authorSharfstein, Susan T.
dc.contributor.authorLinhardt, Robert J.
dc.date2013
dc.date.accessioned2022-06-21T18:41:06Z
dc.date.available2022-06-21T18:41:06Z
dc.date.issued2013-12-27
dc.identifier.citationBioengineered Chinese hamster ovary cells with Golgi-targeted 3-O-sulfotransferase-1 biosynthesize heparan sulfate with an antithrombin binding site, P. Datta, G. Li, B. Yang, X. Zhao, J.- Y. Baik, T. R. Gemmill, S. T. Sharfstein, R. J. Linhardt, Journal of Biological Chemistry, 288, 37308–37318, 2013.
dc.identifier.issn1083351X
dc.identifier.issn219258
dc.identifier.urihttps://hdl.handle.net/20.500.13015/5102
dc.identifier.urihttps://doi.org/10.1074/jbc.M113.519033
dc.descriptionJournal of Biological Chemistry, 288, 37308–37318
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractHS3st1 (heparan sulfate 3-O-sulfotransferase isoform-1) is a critical enzyme involved in the biosynthesis of the antithrombin III (AT)-binding site in the biopharmaceutical drug heparin. Heparin is a highly sulfated glycosaminoglycan that shares a common biosynthetic pathway with heparan sulfate (HS). Although only granulated cells, such as mast cells, biosynthesize heparin, all animal cells are capable of biosynthesizing HS. As part of an effort to bioengineer CHO cells to produce heparin, we previously showed that the introduction of both HS3st1 and NDST2 (N-deacetylase/N-sulfotransferase isoform-2) afforded HS with a very low level of anticoagulant activity. This study demonstrated that untargeted HS3st1 is broadly distributed throughout CHO cells and forms no detectable AT-binding sites, whereas Golgi-targeted HS3st1 localizes in the Golgi and results in the formation of a single type of AT-binding site and high anti-factor Xa activity (137 ± 36 units/mg). Moreover, stable overexpression of HS3st1 also results in up-regulation of 2-O-, 6-O-, and N-sulfo group-containing disaccharides, further emphasizing a previously unknown concerted interplay between the HS biosynthetic enzymes and suggesting the need to control the expression level of all of the biosynthetic enzymes to produce heparin in CHO cells.
dc.languageen_US
dc.language.isoENG
dc.publisherThe American Society for Biochemistry and Molecular Biology (ASBMB) and Elsevier
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofJournal of Biological Chemistry
dc.relation.urihttps://harc.rpi.edu/
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subjectBiology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleBioengineered Chinese hamster ovary cells with Golgi-targeted 3-O-sulfotransferase-1 biosynthesize heparan sulfate with an antithrombin binding siteen_US
dc.typeArticle
dcterms.accessRightsA full text version is available in DSpace@RPI
dcterms.accessRightsOpen Access
dcterms.isPartOfJournal
dcterms.isVersionOfhttps://doi.org/10.1074/jbc.M113.519033
dc.rights.holderCC BY : this license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. Credit must be given to the authors and the original work must be properly cited.
dc.creator.identifierhttps://orcid.org/0000-0003-2219-5833
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
rpi.description.pages37308-37318
rpi.description.volume288


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