Engineering O -glycosylation in modified N -linked oligosaccharide (Man 12 GlcNAc 2 ∼Man 16 GlcNAc 2 ) Pichia pastoris strains
Yeast have been engineered for the production of therapeutic glycoproteins with humanized -linked oligosaccharides. Both - and -linked oligosaccharides engineered yeast have been attractive prospects, since yeast-specific -mannosylated proteins were reported to induce an aberrant immune response and...
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| Veröffentlicht in: | RSC advances 2019-03, Vol.9 (15), p.8246-8252 |
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| creator | Li, Siqiang Sun, Peng Gong, Xin Chang, Shaohong Li, Enzhong Xu, Yuanhong Wu, Jun Liu, Bo |
| description | Yeast have been engineered for the production of therapeutic glycoproteins with humanized
-linked oligosaccharides. Both
- and
-linked oligosaccharides engineered yeast have been attractive prospects, since yeast-specific
-mannosylated proteins were reported to induce an aberrant immune response and alter pharmacokinetics
. In the present study, we genetically manipulated
-glycosylation by disrupting
-mannosyltransferase
and
in a low-mannose type
-linked oligosaccharide (Man
GlcNAc
∼Man
GlcNAc
) engineered
strain to produce therapeutic glycoproteins. The
-mannosyltransferase
mutant produces anti-Her-2 antibodies with reduced
-linked oligosaccharides and protein degradation, but this strain exhibited growth defects. However, the deletion of
-mannosyltransferase
individually has a minimal effect on
-glycosylation, degradation of the anti-Her-2 antibody, and strain growth. Thus, by disrupting
-mannosyltransferase
in an
-glycosylation engineered
strain, we generated an effective glycoengineered
strain to effectively produce therapeutic glycoproteins with both engineered
- and
-linked oligosaccharides. |
| doi_str_mv | 10.1039/c8ra08121b |
| format | Article |
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-linked oligosaccharides. Both
- and
-linked oligosaccharides engineered yeast have been attractive prospects, since yeast-specific
-mannosylated proteins were reported to induce an aberrant immune response and alter pharmacokinetics
. In the present study, we genetically manipulated
-glycosylation by disrupting
-mannosyltransferase
and
in a low-mannose type
-linked oligosaccharide (Man
GlcNAc
∼Man
GlcNAc
) engineered
strain to produce therapeutic glycoproteins. The
-mannosyltransferase
mutant produces anti-Her-2 antibodies with reduced
-linked oligosaccharides and protein degradation, but this strain exhibited growth defects. However, the deletion of
-mannosyltransferase
individually has a minimal effect on
-glycosylation, degradation of the anti-Her-2 antibody, and strain growth. Thus, by disrupting
-mannosyltransferase
in an
-glycosylation engineered
strain, we generated an effective glycoengineered
strain to effectively produce therapeutic glycoproteins with both engineered
- and
-linked oligosaccharides.</description><identifier>ISSN: 2046-2069</identifier><identifier>EISSN: 2046-2069</identifier><identifier>DOI: 10.1039/c8ra08121b</identifier><identifier>PMID: 35518704</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Antibodies ; Chemistry ; Degradation ; Deletion ; Disruption ; Genetic engineering ; Glycoproteins ; Immune system ; In vivo methods and tests ; Mannose ; Oligosaccharides ; Pharmacology ; Proteins ; Yeast</subject><ispartof>RSC advances, 2019-03, Vol.9 (15), p.8246-8252</ispartof><rights>This journal is © The Royal Society of Chemistry.</rights><rights>Copyright Royal Society of Chemistry 2019</rights><rights>This journal is © The Royal Society of Chemistry 2019 The Royal Society of Chemistry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c321b-c018dfaa52797823b67fed3049869ec1b1fc95074d68a9fe7b942ed99cd8f0d83</citedby><cites>FETCH-LOGICAL-c321b-c018dfaa52797823b67fed3049869ec1b1fc95074d68a9fe7b942ed99cd8f0d83</cites><orcidid>0000-0003-4184-7972</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061240/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061240/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35518704$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Siqiang</creatorcontrib><creatorcontrib>Sun, Peng</creatorcontrib><creatorcontrib>Gong, Xin</creatorcontrib><creatorcontrib>Chang, Shaohong</creatorcontrib><creatorcontrib>Li, Enzhong</creatorcontrib><creatorcontrib>Xu, Yuanhong</creatorcontrib><creatorcontrib>Wu, Jun</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><title>Engineering O -glycosylation in modified N -linked oligosaccharide (Man 12 GlcNAc 2 ∼Man 16 GlcNAc 2 ) Pichia pastoris strains</title><title>RSC advances</title><addtitle>RSC Adv</addtitle><description>Yeast have been engineered for the production of therapeutic glycoproteins with humanized
-linked oligosaccharides. Both
- and
-linked oligosaccharides engineered yeast have been attractive prospects, since yeast-specific
-mannosylated proteins were reported to induce an aberrant immune response and alter pharmacokinetics
. In the present study, we genetically manipulated
-glycosylation by disrupting
-mannosyltransferase
and
in a low-mannose type
-linked oligosaccharide (Man
GlcNAc
∼Man
GlcNAc
) engineered
strain to produce therapeutic glycoproteins. The
-mannosyltransferase
mutant produces anti-Her-2 antibodies with reduced
-linked oligosaccharides and protein degradation, but this strain exhibited growth defects. However, the deletion of
-mannosyltransferase
individually has a minimal effect on
-glycosylation, degradation of the anti-Her-2 antibody, and strain growth. Thus, by disrupting
-mannosyltransferase
in an
-glycosylation engineered
strain, we generated an effective glycoengineered
strain to effectively produce therapeutic glycoproteins with both engineered
- and
-linked oligosaccharides.</description><subject>Antibodies</subject><subject>Chemistry</subject><subject>Degradation</subject><subject>Deletion</subject><subject>Disruption</subject><subject>Genetic engineering</subject><subject>Glycoproteins</subject><subject>Immune system</subject><subject>In vivo methods and tests</subject><subject>Mannose</subject><subject>Oligosaccharides</subject><subject>Pharmacology</subject><subject>Proteins</subject><subject>Yeast</subject><issn>2046-2069</issn><issn>2046-2069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpVUctKAzEUDaJY0W78AAm4UWE0ycxkko1Qiy-oVkTXIZNkptFpUpNW6M6lH-XX-CWOtr7u5l7uPZxzLgeAbYwOMUr5kWJBIoYJLlfABkEZTQiifPXP3AHdGB9QWzTHhOJ10EnzHLMCZRvg5dTV1hkTrKvhECZ1M1c-zhs5td5B6-DYa1tZo-E1TBrrHtvJN7b2USo1ksFqA_eupIOYwPNGXfcUJPD99e1rRX9X-_DGqpGVcCLj1AcbYZwGaV3cAmuVbKLpLvsmuD87vetfJIPh-WW_N0hU2v6WKISZrqTMScELRtKSFpXRKco4o9woXOJK8RwVmaZM8soUJc-I0ZwrzSqkWboJjhe8k1k5NloZ1-o3YhLsWIa58NKK_xdnR6L2z4IjikmGWoLdJUHwTzMTp-LBz4JrPQuCOc4QStmnzMECpYKPMZjqRwEj8RmY6LPb3ldgJy1456-nH-h3POkHN8WQeQ</recordid><startdate>20190312</startdate><enddate>20190312</enddate><creator>Li, Siqiang</creator><creator>Sun, Peng</creator><creator>Gong, Xin</creator><creator>Chang, Shaohong</creator><creator>Li, Enzhong</creator><creator>Xu, Yuanhong</creator><creator>Wu, Jun</creator><creator>Liu, Bo</creator><general>Royal Society of Chemistry</general><general>The Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4184-7972</orcidid></search><sort><creationdate>20190312</creationdate><title>Engineering O -glycosylation in modified N -linked oligosaccharide (Man 12 GlcNAc 2 ∼Man 16 GlcNAc 2 ) Pichia pastoris strains</title><author>Li, Siqiang ; Sun, Peng ; Gong, Xin ; Chang, Shaohong ; Li, Enzhong ; Xu, Yuanhong ; Wu, Jun ; Liu, Bo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c321b-c018dfaa52797823b67fed3049869ec1b1fc95074d68a9fe7b942ed99cd8f0d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antibodies</topic><topic>Chemistry</topic><topic>Degradation</topic><topic>Deletion</topic><topic>Disruption</topic><topic>Genetic engineering</topic><topic>Glycoproteins</topic><topic>Immune system</topic><topic>In vivo methods and tests</topic><topic>Mannose</topic><topic>Oligosaccharides</topic><topic>Pharmacology</topic><topic>Proteins</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Siqiang</creatorcontrib><creatorcontrib>Sun, Peng</creatorcontrib><creatorcontrib>Gong, Xin</creatorcontrib><creatorcontrib>Chang, Shaohong</creatorcontrib><creatorcontrib>Li, Enzhong</creatorcontrib><creatorcontrib>Xu, Yuanhong</creatorcontrib><creatorcontrib>Wu, Jun</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>RSC advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Siqiang</au><au>Sun, Peng</au><au>Gong, Xin</au><au>Chang, Shaohong</au><au>Li, Enzhong</au><au>Xu, Yuanhong</au><au>Wu, Jun</au><au>Liu, Bo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Engineering O -glycosylation in modified N -linked oligosaccharide (Man 12 GlcNAc 2 ∼Man 16 GlcNAc 2 ) Pichia pastoris strains</atitle><jtitle>RSC advances</jtitle><addtitle>RSC Adv</addtitle><date>2019-03-12</date><risdate>2019</risdate><volume>9</volume><issue>15</issue><spage>8246</spage><epage>8252</epage><pages>8246-8252</pages><issn>2046-2069</issn><eissn>2046-2069</eissn><abstract>Yeast have been engineered for the production of therapeutic glycoproteins with humanized
-linked oligosaccharides. Both
- and
-linked oligosaccharides engineered yeast have been attractive prospects, since yeast-specific
-mannosylated proteins were reported to induce an aberrant immune response and alter pharmacokinetics
. In the present study, we genetically manipulated
-glycosylation by disrupting
-mannosyltransferase
and
in a low-mannose type
-linked oligosaccharide (Man
GlcNAc
∼Man
GlcNAc
) engineered
strain to produce therapeutic glycoproteins. The
-mannosyltransferase
mutant produces anti-Her-2 antibodies with reduced
-linked oligosaccharides and protein degradation, but this strain exhibited growth defects. However, the deletion of
-mannosyltransferase
individually has a minimal effect on
-glycosylation, degradation of the anti-Her-2 antibody, and strain growth. Thus, by disrupting
-mannosyltransferase
in an
-glycosylation engineered
strain, we generated an effective glycoengineered
strain to effectively produce therapeutic glycoproteins with both engineered
- and
-linked oligosaccharides.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>35518704</pmid><doi>10.1039/c8ra08121b</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-4184-7972</orcidid><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; PubMed Central Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Antibodies Chemistry Degradation Deletion Disruption Genetic engineering Glycoproteins Immune system In vivo methods and tests Mannose Oligosaccharides Pharmacology Proteins Yeast |
| title | Engineering O -glycosylation in modified N -linked oligosaccharide (Man 12 GlcNAc 2 ∼Man 16 GlcNAc 2 ) Pichia pastoris strains |
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