Comprehensive characterization of two different Nicotiana tabacum cell lines leads to doubled GFP and HA protein production by media optimization
For over two decades, plant cell cultures have been a promising research platform to express recombinant and therapeutic proteins such as hormones, growth factors, full-size antibodies and antigens. Chosen as a good host for manufacturing recombinant proteins, the Nicotiana tabacum L. cv. Bright Yel...
Gespeichert in:
| Veröffentlicht in: | Journal of bioscience and bioengineering 2012-02, Vol.113 (2), p.242-248 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 248 |
|---|---|
| container_issue | 2 |
| container_start_page | 242 |
| container_title | Journal of bioscience and bioengineering |
| container_volume | 113 |
| creator | Ullisch, David A. Müller, Christina A. Maibaum, Sabrina Kirchhoff, Janina Schiermeyer, Andreas Schillberg, Stefan Roberts, Jean L. Treffenfeldt, Wiltrud Büchs, Jochen |
| description | For over two decades, plant cell cultures have been a promising research platform to express recombinant and therapeutic proteins such as hormones, growth factors, full-size antibodies and antigens. Chosen as a good host for manufacturing recombinant proteins, the Nicotiana tabacum L. cv. Bright Yellow 2 (BY-2) cell line has been studied in shake flasks by offline analysis of only a few growth parameters. The objective of this study is to comprehensively characterize the growth of a transgenic BY-2 cell line and to investigate the expression profile of the model protein GFP. Based on the correlations between nutrient consumption, cell growth and product formation, the intention is to improve the standard MS-medium. Hereby, multiple growth parameters were analyzed offline and online by using a respiration activity monitoring system (RAMOS). A reproducibly observed shift of the oxygen transfer rate (OTR) could be identified to indicate ammonium depletion in the medium. Concurrent with this ammonium depletion, the total protein concentration began to decrease. After the MS-medium was improved, the GFP concentration nearly doubled. When this improved ammonium enriched medium was applied to another transgenic tobacco cell line similar improvements to the amount of the glycoprotein influenza hemagglutinin (HA) produced by Nicotiana tabacum NT-1 cells could be achieved. Ultimately, this combined offline and online analysis can be successfully used for further cell line characterization and media optimization to improve growth and boost target product formation. |
| doi_str_mv | 10.1016/j.jbiosc.2011.09.022 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_926883290</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1389172311003951</els_id><sourcerecordid>926883290</sourcerecordid><originalsourceid>FETCH-LOGICAL-c540t-eaff2ca60e5f106f01f216be31f8c1a7d32586885bbd5ac095979b0b7db2598a3</originalsourceid><addsrcrecordid>eNqNkUFv1DAQhSMEoqXwDxD4UnHKYjtxEl-QqhVtkSpAgp6tsTOmXiXxYjtF5V_wj-s0C9wQp_Hhe_Oe5xXFS0Y3jLLm7W6z085Hs-GUsQ2VG8r5o-KYVXVb1jVnj5d3J0vW8uqoeBbjjlLW0pY9LY44p0JIJo-LX1s_7gPe4BTdLRJzAwFMwuB-QnJ-It6S9MOT3lmLAadEPjrjk4MJSAINZh6JwWEgg5swkgGhjyRl3s96wJ5cnH8mMPXk8ozsg0_opmX2s3lYru_IiL0D4vfJjQfL58UTC0PEF4d5Ulyfv_-6vSyvPl182J5dlUbUNJUI1nIDDUVhGW0sZZazRmPFbGcYtH3FRdd0ndC6F2CoFLKVmuq211zIDqqT4s26Nwf6PmNManRx-QtM6OeoJM_qikv6HySrOZetyGS9kib4GANatQ9uhHCnGFVLa2qn1tbU0pqiUuXWsuzVwWDW-SB_RL9rysDpAYBoYLABJuPiX040GeJL0tcrZ8Er-BYyc_0lOzWUUl5JWWfi3UpgPu2tw6CicTiZXENAk1Tv3b-z3gPO0sL1</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>921422975</pqid></control><display><type>article</type><title>Comprehensive characterization of two different Nicotiana tabacum cell lines leads to doubled GFP and HA protein production by media optimization</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Ullisch, David A. ; Müller, Christina A. ; Maibaum, Sabrina ; Kirchhoff, Janina ; Schiermeyer, Andreas ; Schillberg, Stefan ; Roberts, Jean L. ; Treffenfeldt, Wiltrud ; Büchs, Jochen</creator><creatorcontrib>Ullisch, David A. ; Müller, Christina A. ; Maibaum, Sabrina ; Kirchhoff, Janina ; Schiermeyer, Andreas ; Schillberg, Stefan ; Roberts, Jean L. ; Treffenfeldt, Wiltrud ; Büchs, Jochen</creatorcontrib><description>For over two decades, plant cell cultures have been a promising research platform to express recombinant and therapeutic proteins such as hormones, growth factors, full-size antibodies and antigens. Chosen as a good host for manufacturing recombinant proteins, the Nicotiana tabacum L. cv. Bright Yellow 2 (BY-2) cell line has been studied in shake flasks by offline analysis of only a few growth parameters. The objective of this study is to comprehensively characterize the growth of a transgenic BY-2 cell line and to investigate the expression profile of the model protein GFP. Based on the correlations between nutrient consumption, cell growth and product formation, the intention is to improve the standard MS-medium. Hereby, multiple growth parameters were analyzed offline and online by using a respiration activity monitoring system (RAMOS). A reproducibly observed shift of the oxygen transfer rate (OTR) could be identified to indicate ammonium depletion in the medium. Concurrent with this ammonium depletion, the total protein concentration began to decrease. After the MS-medium was improved, the GFP concentration nearly doubled. When this improved ammonium enriched medium was applied to another transgenic tobacco cell line similar improvements to the amount of the glycoprotein influenza hemagglutinin (HA) produced by Nicotiana tabacum NT-1 cells could be achieved. Ultimately, this combined offline and online analysis can be successfully used for further cell line characterization and media optimization to improve growth and boost target product formation.</description><identifier>ISSN: 1389-1723</identifier><identifier>EISSN: 1347-4421</identifier><identifier>DOI: 10.1016/j.jbiosc.2011.09.022</identifier><identifier>PMID: 22055919</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>antibodies ; antigens ; Biological and medical sciences ; biopharmaceuticals ; Biotechnology ; BY-2 cells ; cell culture ; cell growth ; containers ; Culture Media - chemistry ; Fundamental and applied biological sciences. Psychology ; glycoproteins ; Green Fluorescent Proteins - biosynthesis ; Green Fluorescent Proteins - genetics ; growth factors ; Hemagglutinin Glycoproteins, Influenza Virus - biosynthesis ; Hemagglutinin Glycoproteins, Influenza Virus - genetics ; hemagglutinins ; hormones ; influenza ; Influenza hemagglutinin ; manufacturing ; Media optimization ; monitoring ; Nicotiana - cytology ; Nicotiana - genetics ; Nicotiana - growth & development ; Nicotiana - metabolism ; Nicotiana tabacum ; Nitrogen source ; oxygen ; Oxygen transfer rate ; Plant cell culture ; Plants, Genetically Modified - cytology ; Plants, Genetically Modified - growth & development ; Plants, Genetically Modified - metabolism ; protein content ; Quaternary Ammonium Compounds - analysis ; recombinant proteins ; Recombinant Proteins - biosynthesis ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; respiration activity monitoring system (RAMOS) ; Shake flasks ; tobacco ; transgenic plants</subject><ispartof>Journal of bioscience and bioengineering, 2012-02, Vol.113 (2), p.242-248</ispartof><rights>2011 The Society for Biotechnology, Japan</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-eaff2ca60e5f106f01f216be31f8c1a7d32586885bbd5ac095979b0b7db2598a3</citedby><cites>FETCH-LOGICAL-c540t-eaff2ca60e5f106f01f216be31f8c1a7d32586885bbd5ac095979b0b7db2598a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jbiosc.2011.09.022$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25619320$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22055919$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ullisch, David A.</creatorcontrib><creatorcontrib>Müller, Christina A.</creatorcontrib><creatorcontrib>Maibaum, Sabrina</creatorcontrib><creatorcontrib>Kirchhoff, Janina</creatorcontrib><creatorcontrib>Schiermeyer, Andreas</creatorcontrib><creatorcontrib>Schillberg, Stefan</creatorcontrib><creatorcontrib>Roberts, Jean L.</creatorcontrib><creatorcontrib>Treffenfeldt, Wiltrud</creatorcontrib><creatorcontrib>Büchs, Jochen</creatorcontrib><title>Comprehensive characterization of two different Nicotiana tabacum cell lines leads to doubled GFP and HA protein production by media optimization</title><title>Journal of bioscience and bioengineering</title><addtitle>J Biosci Bioeng</addtitle><description>For over two decades, plant cell cultures have been a promising research platform to express recombinant and therapeutic proteins such as hormones, growth factors, full-size antibodies and antigens. Chosen as a good host for manufacturing recombinant proteins, the Nicotiana tabacum L. cv. Bright Yellow 2 (BY-2) cell line has been studied in shake flasks by offline analysis of only a few growth parameters. The objective of this study is to comprehensively characterize the growth of a transgenic BY-2 cell line and to investigate the expression profile of the model protein GFP. Based on the correlations between nutrient consumption, cell growth and product formation, the intention is to improve the standard MS-medium. Hereby, multiple growth parameters were analyzed offline and online by using a respiration activity monitoring system (RAMOS). A reproducibly observed shift of the oxygen transfer rate (OTR) could be identified to indicate ammonium depletion in the medium. Concurrent with this ammonium depletion, the total protein concentration began to decrease. After the MS-medium was improved, the GFP concentration nearly doubled. When this improved ammonium enriched medium was applied to another transgenic tobacco cell line similar improvements to the amount of the glycoprotein influenza hemagglutinin (HA) produced by Nicotiana tabacum NT-1 cells could be achieved. Ultimately, this combined offline and online analysis can be successfully used for further cell line characterization and media optimization to improve growth and boost target product formation.</description><subject>antibodies</subject><subject>antigens</subject><subject>Biological and medical sciences</subject><subject>biopharmaceuticals</subject><subject>Biotechnology</subject><subject>BY-2 cells</subject><subject>cell culture</subject><subject>cell growth</subject><subject>containers</subject><subject>Culture Media - chemistry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>glycoproteins</subject><subject>Green Fluorescent Proteins - biosynthesis</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>growth factors</subject><subject>Hemagglutinin Glycoproteins, Influenza Virus - biosynthesis</subject><subject>Hemagglutinin Glycoproteins, Influenza Virus - genetics</subject><subject>hemagglutinins</subject><subject>hormones</subject><subject>influenza</subject><subject>Influenza hemagglutinin</subject><subject>manufacturing</subject><subject>Media optimization</subject><subject>monitoring</subject><subject>Nicotiana - cytology</subject><subject>Nicotiana - genetics</subject><subject>Nicotiana - growth & development</subject><subject>Nicotiana - metabolism</subject><subject>Nicotiana tabacum</subject><subject>Nitrogen source</subject><subject>oxygen</subject><subject>Oxygen transfer rate</subject><subject>Plant cell culture</subject><subject>Plants, Genetically Modified - cytology</subject><subject>Plants, Genetically Modified - growth & development</subject><subject>Plants, Genetically Modified - metabolism</subject><subject>protein content</subject><subject>Quaternary Ammonium Compounds - analysis</subject><subject>recombinant proteins</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>respiration activity monitoring system (RAMOS)</subject><subject>Shake flasks</subject><subject>tobacco</subject><subject>transgenic plants</subject><issn>1389-1723</issn><issn>1347-4421</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUFv1DAQhSMEoqXwDxD4UnHKYjtxEl-QqhVtkSpAgp6tsTOmXiXxYjtF5V_wj-s0C9wQp_Hhe_Oe5xXFS0Y3jLLm7W6z085Hs-GUsQ2VG8r5o-KYVXVb1jVnj5d3J0vW8uqoeBbjjlLW0pY9LY44p0JIJo-LX1s_7gPe4BTdLRJzAwFMwuB-QnJ-It6S9MOT3lmLAadEPjrjk4MJSAINZh6JwWEgg5swkgGhjyRl3s96wJ5cnH8mMPXk8ozsg0_opmX2s3lYru_IiL0D4vfJjQfL58UTC0PEF4d5Ulyfv_-6vSyvPl182J5dlUbUNJUI1nIDDUVhGW0sZZazRmPFbGcYtH3FRdd0ndC6F2CoFLKVmuq211zIDqqT4s26Nwf6PmNManRx-QtM6OeoJM_qikv6HySrOZetyGS9kib4GANatQ9uhHCnGFVLa2qn1tbU0pqiUuXWsuzVwWDW-SB_RL9rysDpAYBoYLABJuPiX040GeJL0tcrZ8Er-BYyc_0lOzWUUl5JWWfi3UpgPu2tw6CicTiZXENAk1Tv3b-z3gPO0sL1</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Ullisch, David A.</creator><creator>Müller, Christina A.</creator><creator>Maibaum, Sabrina</creator><creator>Kirchhoff, Janina</creator><creator>Schiermeyer, Andreas</creator><creator>Schillberg, Stefan</creator><creator>Roberts, Jean L.</creator><creator>Treffenfeldt, Wiltrud</creator><creator>Büchs, Jochen</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20120201</creationdate><title>Comprehensive characterization of two different Nicotiana tabacum cell lines leads to doubled GFP and HA protein production by media optimization</title><author>Ullisch, David A. ; Müller, Christina A. ; Maibaum, Sabrina ; Kirchhoff, Janina ; Schiermeyer, Andreas ; Schillberg, Stefan ; Roberts, Jean L. ; Treffenfeldt, Wiltrud ; Büchs, Jochen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-eaff2ca60e5f106f01f216be31f8c1a7d32586885bbd5ac095979b0b7db2598a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>antibodies</topic><topic>antigens</topic><topic>Biological and medical sciences</topic><topic>biopharmaceuticals</topic><topic>Biotechnology</topic><topic>BY-2 cells</topic><topic>cell culture</topic><topic>cell growth</topic><topic>containers</topic><topic>Culture Media - chemistry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>glycoproteins</topic><topic>Green Fluorescent Proteins - biosynthesis</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>growth factors</topic><topic>Hemagglutinin Glycoproteins, Influenza Virus - biosynthesis</topic><topic>Hemagglutinin Glycoproteins, Influenza Virus - genetics</topic><topic>hemagglutinins</topic><topic>hormones</topic><topic>influenza</topic><topic>Influenza hemagglutinin</topic><topic>manufacturing</topic><topic>Media optimization</topic><topic>monitoring</topic><topic>Nicotiana - cytology</topic><topic>Nicotiana - genetics</topic><topic>Nicotiana - growth & development</topic><topic>Nicotiana - metabolism</topic><topic>Nicotiana tabacum</topic><topic>Nitrogen source</topic><topic>oxygen</topic><topic>Oxygen transfer rate</topic><topic>Plant cell culture</topic><topic>Plants, Genetically Modified - cytology</topic><topic>Plants, Genetically Modified - growth & development</topic><topic>Plants, Genetically Modified - metabolism</topic><topic>protein content</topic><topic>Quaternary Ammonium Compounds - analysis</topic><topic>recombinant proteins</topic><topic>Recombinant Proteins - biosynthesis</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - metabolism</topic><topic>respiration activity monitoring system (RAMOS)</topic><topic>Shake flasks</topic><topic>tobacco</topic><topic>transgenic plants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ullisch, David A.</creatorcontrib><creatorcontrib>Müller, Christina A.</creatorcontrib><creatorcontrib>Maibaum, Sabrina</creatorcontrib><creatorcontrib>Kirchhoff, Janina</creatorcontrib><creatorcontrib>Schiermeyer, Andreas</creatorcontrib><creatorcontrib>Schillberg, Stefan</creatorcontrib><creatorcontrib>Roberts, Jean L.</creatorcontrib><creatorcontrib>Treffenfeldt, Wiltrud</creatorcontrib><creatorcontrib>Büchs, Jochen</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of bioscience and bioengineering</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ullisch, David A.</au><au>Müller, Christina A.</au><au>Maibaum, Sabrina</au><au>Kirchhoff, Janina</au><au>Schiermeyer, Andreas</au><au>Schillberg, Stefan</au><au>Roberts, Jean L.</au><au>Treffenfeldt, Wiltrud</au><au>Büchs, Jochen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comprehensive characterization of two different Nicotiana tabacum cell lines leads to doubled GFP and HA protein production by media optimization</atitle><jtitle>Journal of bioscience and bioengineering</jtitle><addtitle>J Biosci Bioeng</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>113</volume><issue>2</issue><spage>242</spage><epage>248</epage><pages>242-248</pages><issn>1389-1723</issn><eissn>1347-4421</eissn><abstract>For over two decades, plant cell cultures have been a promising research platform to express recombinant and therapeutic proteins such as hormones, growth factors, full-size antibodies and antigens. Chosen as a good host for manufacturing recombinant proteins, the Nicotiana tabacum L. cv. Bright Yellow 2 (BY-2) cell line has been studied in shake flasks by offline analysis of only a few growth parameters. The objective of this study is to comprehensively characterize the growth of a transgenic BY-2 cell line and to investigate the expression profile of the model protein GFP. Based on the correlations between nutrient consumption, cell growth and product formation, the intention is to improve the standard MS-medium. Hereby, multiple growth parameters were analyzed offline and online by using a respiration activity monitoring system (RAMOS). A reproducibly observed shift of the oxygen transfer rate (OTR) could be identified to indicate ammonium depletion in the medium. Concurrent with this ammonium depletion, the total protein concentration began to decrease. After the MS-medium was improved, the GFP concentration nearly doubled. When this improved ammonium enriched medium was applied to another transgenic tobacco cell line similar improvements to the amount of the glycoprotein influenza hemagglutinin (HA) produced by Nicotiana tabacum NT-1 cells could be achieved. Ultimately, this combined offline and online analysis can be successfully used for further cell line characterization and media optimization to improve growth and boost target product formation.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>22055919</pmid><doi>10.1016/j.jbiosc.2011.09.022</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1389-1723 |
| ispartof | Journal of bioscience and bioengineering, 2012-02, Vol.113 (2), p.242-248 |
| issn | 1389-1723 1347-4421 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_926883290 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | antibodies antigens Biological and medical sciences biopharmaceuticals Biotechnology BY-2 cells cell culture cell growth containers Culture Media - chemistry Fundamental and applied biological sciences. Psychology glycoproteins Green Fluorescent Proteins - biosynthesis Green Fluorescent Proteins - genetics growth factors Hemagglutinin Glycoproteins, Influenza Virus - biosynthesis Hemagglutinin Glycoproteins, Influenza Virus - genetics hemagglutinins hormones influenza Influenza hemagglutinin manufacturing Media optimization monitoring Nicotiana - cytology Nicotiana - genetics Nicotiana - growth & development Nicotiana - metabolism Nicotiana tabacum Nitrogen source oxygen Oxygen transfer rate Plant cell culture Plants, Genetically Modified - cytology Plants, Genetically Modified - growth & development Plants, Genetically Modified - metabolism protein content Quaternary Ammonium Compounds - analysis recombinant proteins Recombinant Proteins - biosynthesis Recombinant Proteins - genetics Recombinant Proteins - metabolism respiration activity monitoring system (RAMOS) Shake flasks tobacco transgenic plants |
| title | Comprehensive characterization of two different Nicotiana tabacum cell lines leads to doubled GFP and HA protein production by media optimization |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T05%3A00%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Comprehensive%20characterization%20of%20two%20different%20Nicotiana%20tabacum%20cell%20lines%20leads%20to%20doubled%20GFP%20and%20HA%20protein%20production%20by%20media%20optimization&rft.jtitle=Journal%20of%20bioscience%20and%20bioengineering&rft.au=Ullisch,%20David%20A.&rft.date=2012-02-01&rft.volume=113&rft.issue=2&rft.spage=242&rft.epage=248&rft.pages=242-248&rft.issn=1389-1723&rft.eissn=1347-4421&rft_id=info:doi/10.1016/j.jbiosc.2011.09.022&rft_dat=%3Cproquest_cross%3E926883290%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=921422975&rft_id=info:pmid/22055919&rft_els_id=S1389172311003951&rfr_iscdi=true |