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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Exploiting Bacterial Glycosylation Machineries for the Synthesis of a Lewis Antigen-containing Glycoprotein<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></title><author><name sortKey="Hug, Isabelle" sort="Hug, Isabelle" uniqKey="Hug I" first="Isabelle" last="Hug">Isabelle Hug</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Zheng, Blake" sort="Zheng, Blake" uniqKey="Zheng B" first="Blake" last="Zheng">Blake Zheng</name><affiliation><nlm:aff id="aff2">Chemistry, University of Alberta, Edmonton, Alberta T6G 2E9, Canada</nlm:aff></affiliation></author><author><name sortKey="Reiz, Bela" sort="Reiz, Bela" uniqKey="Reiz B" first="Bela" last="Reiz">Bela Reiz</name><affiliation><nlm:aff id="aff2">Chemistry, University of Alberta, Edmonton, Alberta T6G 2E9, Canada</nlm:aff></affiliation></author><author><name sortKey="Whittal, Randy M" sort="Whittal, Randy M" uniqKey="Whittal R" first="Randy M." last="Whittal">Randy M. Whittal</name><affiliation><nlm:aff id="aff2">Chemistry, University of Alberta, Edmonton, Alberta T6G 2E9, Canada</nlm:aff></affiliation></author><author><name sortKey="Fentabil, Messele A" sort="Fentabil, Messele A" uniqKey="Fentabil M" first="Messele A." last="Fentabil">Messele A. Fentabil</name><affiliation><nlm:aff id="aff2">Chemistry, University of Alberta, Edmonton, Alberta T6G 2E9, Canada</nlm:aff></affiliation></author><author><name sortKey="Klassen, John S" sort="Klassen, John S" uniqKey="Klassen J" first="John S." last="Klassen">John S. Klassen</name><affiliation><nlm:aff id="aff2">Chemistry, University of Alberta, Edmonton, Alberta T6G 2E9, Canada</nlm:aff></affiliation></author><author><name sortKey="Feldman, Mario F" sort="Feldman, Mario F" uniqKey="Feldman M" first="Mario F." last="Feldman">Mario F. Feldman</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21878645</idno><idno type="pmc">3199530</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199530</idno><idno type="RBID">PMC:3199530</idno><idno type="doi">10.1074/jbc.M111.287755</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000130</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000130</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Exploiting Bacterial Glycosylation Machineries for the Synthesis of a Lewis Antigen-containing Glycoprotein<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></title><author><name sortKey="Hug, Isabelle" sort="Hug, Isabelle" uniqKey="Hug I" first="Isabelle" last="Hug">Isabelle Hug</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Zheng, Blake" sort="Zheng, Blake" uniqKey="Zheng B" first="Blake" last="Zheng">Blake Zheng</name><affiliation><nlm:aff id="aff2">Chemistry, University of Alberta, Edmonton, Alberta T6G 2E9, Canada</nlm:aff></affiliation></author><author><name sortKey="Reiz, Bela" sort="Reiz, Bela" uniqKey="Reiz B" first="Bela" last="Reiz">Bela Reiz</name><affiliation><nlm:aff id="aff2">Chemistry, University of Alberta, Edmonton, Alberta T6G 2E9, Canada</nlm:aff></affiliation></author><author><name sortKey="Whittal, Randy M" sort="Whittal, Randy M" uniqKey="Whittal R" first="Randy M." last="Whittal">Randy M. Whittal</name><affiliation><nlm:aff id="aff2">Chemistry, University of Alberta, Edmonton, Alberta T6G 2E9, Canada</nlm:aff></affiliation></author><author><name sortKey="Fentabil, Messele A" sort="Fentabil, Messele A" uniqKey="Fentabil M" first="Messele A." last="Fentabil">Messele A. Fentabil</name><affiliation><nlm:aff id="aff2">Chemistry, University of Alberta, Edmonton, Alberta T6G 2E9, Canada</nlm:aff></affiliation></author><author><name sortKey="Klassen, John S" sort="Klassen, John S" uniqKey="Klassen J" first="John S." last="Klassen">John S. Klassen</name><affiliation><nlm:aff id="aff2">Chemistry, University of Alberta, Edmonton, Alberta T6G 2E9, Canada</nlm:aff></affiliation></author><author><name sortKey="Feldman, Mario F" sort="Feldman, Mario F" uniqKey="Feldman M" first="Mario F." last="Feldman">Mario F. Feldman</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> Bacterial glycosylation systems appear to be ideal for glycoengineering purposes.</p><p><bold>Results:</bold> A Lewis x containing glycoprotein was synthesized using bacterial enzymes from four different species using <italic>in vivo</italic> and <italic>in vitro</italic> steps.</p><p><bold>Conclusion:</bold> Glycosylation systems in bacteria open new avenues for the production of engineered glycoproteins.</p><p><bold>Significance:</bold> Bacterial glycoengineering is a promising technology for the production of therapeutically valuable glycoproteins with expected high precision and low cost.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Biol Chem</journal-id><journal-id journal-id-type="hwp">jbc</journal-id><journal-id journal-id-type="pmc">jbc</journal-id><journal-id journal-id-type="publisher-id">JBC</journal-id><journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0021-9258</issn><issn pub-type="epub">1083-351X</issn><publisher><publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name><publisher-loc>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21878645</article-id><article-id pub-id-type="pmc">3199530</article-id><article-id pub-id-type="publisher-id">M111.287755</article-id><article-id pub-id-type="doi">10.1074/jbc.M111.287755</article-id><article-categories><subj-group subj-group-type="heading"><subject>Glycobiology and Extracellular Matrices</subject></subj-group></article-categories><title-group><article-title>Exploiting Bacterial Glycosylation Machineries for the Synthesis of a Lewis Antigen-containing Glycoprotein<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></article-title><alt-title alt-title-type="short">Engineering a Lewis x Glycoprotein Using Bacterial Enzymes</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Hug</surname><given-names>Isabelle</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="author-notes" rid="FN3"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zheng</surname><given-names>Blake</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Reiz</surname><given-names>Bela</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Whittal</surname><given-names>Randy M.</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fentabil</surname><given-names>Messele A.</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Klassen</surname><given-names>John S.</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Feldman</surname><given-names>Mario F.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1">From the Departments of<label>‡</label>Biological Sciences and</aff><aff id="aff2"><label>§</label>Chemistry, University of Alberta, Edmonton, Alberta T6G 2E9, Canada</aff></contrib-group><author-notes><corresp id="cor1"><label>2</label> Alberta Heritage Foundation for Medical Research (AHFMR) scholar and a Canadian Institutes of Health Research new investigator. To whom correspondence should be addressed: <addr-line>405 Biological Sciences Bldg., University of Alberta, Edmonton, Alberta T6G 2E9, Canada.</addr-line> Tel.: <phone>780-492-6105</phone>; Fax: <fax>780-492-9234</fax>; E-mail: <email>mfeldman@ualberta.ca</email>.</corresp><fn fn-type="present-address" id="FN3"><label>1</label><p>Present address: Biozentrum, University of Basel, Switzerland.</p></fn></author-notes><pub-date pub-type="ppub"><day>28</day><month>10</month><year>2011</year></pub-date><pub-date pub-type="epub"><day>30</day><month>8</month><year>2011</year></pub-date><volume>286</volume><issue>43</issue><fpage>37887</fpage><lpage>37894</lpage><history><date date-type="received"><day>3</day><month>8</month><year>2011</year></date><date date-type="rev-recd"><day>26</day><month>8</month><year>2011</year></date></history><permissions><copyright-statement>© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement><copyright-year>2011</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc04311037887.pdf"></self-uri><abstract abstract-type="teaser"><p><bold>Background:</bold> Bacterial glycosylation systems appear to be ideal for glycoengineering purposes.</p><p><bold>Results:</bold> A Lewis x containing glycoprotein was synthesized using bacterial enzymes from four different species using <italic>in vivo</italic> and <italic>in vitro</italic> steps.</p><p><bold>Conclusion:</bold> Glycosylation systems in bacteria open new avenues for the production of engineered glycoproteins.</p><p><bold>Significance:</bold> Bacterial glycoengineering is a promising technology for the production of therapeutically valuable glycoproteins with expected high precision and low cost.</p></abstract><abstract><p>Glycoproteins constitute a class of compounds of increasing importance for pharmaceutical applications. The manipulation of bacterial protein glycosylation systems from Gram-negative bacteria for the synthesis of recombinant glycoproteins is a promising alternative to the current production methods. Proteins carrying Lewis antigens have been shown to have potential applications for the treatment of diverse autoimmune diseases. In this work, we developed a mixed approach consisting of <italic>in vivo</italic> and <italic>in vitro</italic> steps for the synthesis of glycoproteins containing the Lewis x antigen. Using glycosyltransferases from <italic>Haemophilus influenzae</italic>, we engineered <italic>Escherichia coli</italic> to assemble a tetrasaccharide on the lipid carrier undecaprenylphosphate. This glycan was transferred <italic>in vivo</italic> from the lipid to a carrier protein by the <italic>Campylobacter jejuni</italic> oligosaccharyltransferase PglB. The glycoprotein was then fucosylated <italic>in vitro</italic> by a truncated fucosyltransferase from <italic>Helicobacter pylori</italic>. Diverse mass spectrometry techniques were used to confirm the structure of the glycan. The strategy presented here could be adapted in the future for the synthesis of diverse glycoproteins. Our experiments demonstrate that bacterial enzymes can be exploited for the production of glycoproteins carrying glycans present in human cells for potential therapeutic applications.</p></abstract><kwd-group><kwd>Glycoconjugate</kwd><kwd>Glycoprotein</kwd><kwd>Glycosylation</kwd><kwd>Glycosyltransferases</kwd><kwd>Helicobacter pylori</kwd><kwd>Bacterial Glycoproteins</kwd><kwd>Fucosyltransferase</kwd><kwd>Glycoengineering</kwd><kwd>Oligosaccharyltansferase</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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