The relationship of metabolic burden to productivity levels in CHO cell lines
The growing demand for recombinant therapeutics has driven biotechnologists to develop new production strategies. One such strategy for increasing the expression of heterologous proteins has focused on enhancing cell‐specific productivity through environmental perturbations. In this work, the effect...
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Veröffentlicht in: | Biotechnology and applied biochemistry 2018-03, Vol.65 (2), p.173-180 |
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creator | Zou, Wu Edros, Raihana Al‐Rubeai, Mohamed |
description | The growing demand for recombinant therapeutics has driven biotechnologists to develop new production strategies. One such strategy for increasing the expression of heterologous proteins has focused on enhancing cell‐specific productivity through environmental perturbations. In this work, the effects of hypothermia, hyperosmolarity, high shear stress, and sodium butyrate treatment on growth and productivity were studied using three (low, medium, and high producing) CHO cell lines that differed in their specific productivities of monoclonal antibody. In all three cell lines, the inhibitory effect of these parameters on proliferation was demonstrated. Additionally, compared to the control, specific productivity was enhanced under all conditions and exhibited a consistent cell line specific pattern, with maximum increases (50–290%) in the low producer, and minimum increases (7–20%) in the high producer. Thus, the high‐producing cell line was less responsive to environmental perturbations than the low‐producing cell line. We hypothesize that this difference is most likely due to the bottleneck associated with a higher metabolic burden caused by higher antibody expression. Increased recombinant mRNA levels and pyruvate carboxylase activities due to low temperature and hyperosmotic stress were found to be positively associated with the metabolic burden. |
doi_str_mv | 10.1002/bab.1574 |
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One such strategy for increasing the expression of heterologous proteins has focused on enhancing cell‐specific productivity through environmental perturbations. In this work, the effects of hypothermia, hyperosmolarity, high shear stress, and sodium butyrate treatment on growth and productivity were studied using three (low, medium, and high producing) CHO cell lines that differed in their specific productivities of monoclonal antibody. In all three cell lines, the inhibitory effect of these parameters on proliferation was demonstrated. Additionally, compared to the control, specific productivity was enhanced under all conditions and exhibited a consistent cell line specific pattern, with maximum increases (50–290%) in the low producer, and minimum increases (7–20%) in the high producer. Thus, the high‐producing cell line was less responsive to environmental perturbations than the low‐producing cell line. We hypothesize that this difference is most likely due to the bottleneck associated with a higher metabolic burden caused by higher antibody expression. Increased recombinant mRNA levels and pyruvate carboxylase activities due to low temperature and hyperosmotic stress were found to be positively associated with the metabolic burden.</description><identifier>ISSN: 0885-4513</identifier><identifier>EISSN: 1470-8744</identifier><identifier>DOI: 10.1002/bab.1574</identifier><identifier>PMID: 28681393</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Biotechnology ; Cell lines ; environmental perturbation ; Gene expression ; GS‐CHO cell line ; Hypothermia ; Low temperature ; metabolic burden ; Metabolism ; Monoclonal antibodies ; monoclonal antibody ; mRNA ; Osmotic pressure ; Productivity ; Proteins ; Pyruvate carboxylase ; Pyruvic acid ; Shear stress ; Sodium ; Sodium butyrate ; specific productivity</subject><ispartof>Biotechnology and applied biochemistry, 2018-03, Vol.65 (2), p.173-180</ispartof><rights>2017 International Union of Biochemistry and Molecular Biology, Inc.</rights><rights>Copyright © 2018 International Union of Biochemistry and Molecular Biology, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3494-353e79d50f0f8b8df4ba15093e52a28d68ef9eba3de5545a844e14e0ee372d9a3</citedby><cites>FETCH-LOGICAL-c3494-353e79d50f0f8b8df4ba15093e52a28d68ef9eba3de5545a844e14e0ee372d9a3</cites><orcidid>0000-0003-1062-2295</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fbab.1574$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fbab.1574$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28681393$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zou, Wu</creatorcontrib><creatorcontrib>Edros, Raihana</creatorcontrib><creatorcontrib>Al‐Rubeai, Mohamed</creatorcontrib><title>The relationship of metabolic burden to productivity levels in CHO cell lines</title><title>Biotechnology and applied biochemistry</title><addtitle>Biotechnol Appl Biochem</addtitle><description>The growing demand for recombinant therapeutics has driven biotechnologists to develop new production strategies. One such strategy for increasing the expression of heterologous proteins has focused on enhancing cell‐specific productivity through environmental perturbations. In this work, the effects of hypothermia, hyperosmolarity, high shear stress, and sodium butyrate treatment on growth and productivity were studied using three (low, medium, and high producing) CHO cell lines that differed in their specific productivities of monoclonal antibody. In all three cell lines, the inhibitory effect of these parameters on proliferation was demonstrated. Additionally, compared to the control, specific productivity was enhanced under all conditions and exhibited a consistent cell line specific pattern, with maximum increases (50–290%) in the low producer, and minimum increases (7–20%) in the high producer. Thus, the high‐producing cell line was less responsive to environmental perturbations than the low‐producing cell line. We hypothesize that this difference is most likely due to the bottleneck associated with a higher metabolic burden caused by higher antibody expression. Increased recombinant mRNA levels and pyruvate carboxylase activities due to low temperature and hyperosmotic stress were found to be positively associated with the metabolic burden.</description><subject>Biotechnology</subject><subject>Cell lines</subject><subject>environmental perturbation</subject><subject>Gene expression</subject><subject>GS‐CHO cell line</subject><subject>Hypothermia</subject><subject>Low temperature</subject><subject>metabolic burden</subject><subject>Metabolism</subject><subject>Monoclonal antibodies</subject><subject>monoclonal antibody</subject><subject>mRNA</subject><subject>Osmotic pressure</subject><subject>Productivity</subject><subject>Proteins</subject><subject>Pyruvate carboxylase</subject><subject>Pyruvic acid</subject><subject>Shear stress</subject><subject>Sodium</subject><subject>Sodium butyrate</subject><subject>specific productivity</subject><issn>0885-4513</issn><issn>1470-8744</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kEFLwzAYhoMobk7BXyABL146kyZZk-M21AnKLvMc0vYry8iambST_Xs7NxUET-_l4eHlQeiakiElJL3PTT6kIuMnqE95RhKZcX6K-kRKkXBBWQ9dxLgihMhMpueol8qRpEyxPnpdLAEHcKaxvo5Lu8G-wmtoTO6dLXDehhJq3Hi8Cb5si8ZubbPDDrbgIrY1ns7muADnsLM1xEt0VhkX4eq4A_T2-LCYzpKX-dPzdPySFIwrnjDBIFOlIBWpZC7LiueGCqIYiNSkshxJqBTkhpUgBBdGcg6UAwFgWVoqwwbo7uDtXr23EBu9tnF_w9Tg26ipoqOM0ozRDr39g658G-runU5JKpggTKlfYRF8jAEqvQl2bcJOU6L3iXWXWO8Td-jNUdjmayh_wO-mHZAcgA_rYPevSE_Gky_hJ8jHg4M</recordid><startdate>201803</startdate><enddate>201803</enddate><creator>Zou, Wu</creator><creator>Edros, Raihana</creator><creator>Al‐Rubeai, Mohamed</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7TB</scope><scope>7TK</scope><scope>7U5</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>L7M</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1062-2295</orcidid></search><sort><creationdate>201803</creationdate><title>The relationship of metabolic burden to productivity levels in CHO cell lines</title><author>Zou, Wu ; 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subjects | Biotechnology Cell lines environmental perturbation Gene expression GS‐CHO cell line Hypothermia Low temperature metabolic burden Metabolism Monoclonal antibodies monoclonal antibody mRNA Osmotic pressure Productivity Proteins Pyruvate carboxylase Pyruvic acid Shear stress Sodium Sodium butyrate specific productivity |
title | The relationship of metabolic burden to productivity levels in CHO cell lines |
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