Advances in improving mammalian cells metabolism for recombinant protein production

Background: The production of recombinant proteins for therapeutic use represents a great impact on the biotechnology industry. In this context, established mammalian cell lines, especially CHO cells, have become a standard system for the production of such proteins. Their ability to properly config...

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Autores principales:	Altamirano,Claudia, Berrios,Julio, Vergara,Mauricio, Becerra,Silvana
Lenguaje:	English
Publicado:	Pontificia Universidad Católica de Valparaíso 2013
Materias:	aerobic glycolysis cell engineering CHO cells glutaminolysis metabolism
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-34582013000300010
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spelling	oai:scielo:S0717-345820130003000102013-08-22Advances in improving mammalian cells metabolism for recombinant protein productionAltamirano,ClaudiaBerrios,JulioVergara,MauricioBecerra,Silvana aerobic glycolysis cell engineering CHO cells glutaminolysis metabolism Background: The production of recombinant proteins for therapeutic use represents a great impact on the biotechnology industry. In this context, established mammalian cell lines, especially CHO cells, have become a standard system for the production of such proteins. Their ability to properly configure and excrete proteins in functional form is an enormous advantage which should be contrasted with their inherent technological limitations. These cell systems exhibit a metabolic behaviour associated with elevated cell proliferation which involves a high consumption of glucose and glutamine, resulting in the rapid depletion of these nutrients in the medium and the accumulation of ammonium and lactate. Both phenomena contribute to the limitation of cell growth, the triggering of apoptotic processes and the loss of quality of the recombinant protein. Results: In this review, the use of alternative substrates and genetic modifications (host cell engineering) are analyzed as tools to overcome those limitations. In general, the results obtained are promising. However, metabolic and physiological phenomena involved in CHO cells are still barely understood. Thus, most of publications are focused on specific modifications rather than giving a systemic perspective. Conclusions: A deeper insight in the integrated understanding of metabolism and cell mechanisms is required in order to define complementary strategies at these two levels, so providing effective means to control nutrients consumption, reduce by-products and increase process productivity.info:eu-repo/semantics/openAccessPontificia Universidad Católica de ValparaísoElectronic Journal of Biotechnology v.16 n.3 20132013-05-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-34582013000300010en10.2225/vol16-issue3-fulltext-2
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	aerobic glycolysis cell engineering CHO cells glutaminolysis metabolism
spellingShingle	aerobic glycolysis cell engineering CHO cells glutaminolysis metabolism Altamirano,Claudia Berrios,Julio Vergara,Mauricio Becerra,Silvana Advances in improving mammalian cells metabolism for recombinant protein production
description	Background: The production of recombinant proteins for therapeutic use represents a great impact on the biotechnology industry. In this context, established mammalian cell lines, especially CHO cells, have become a standard system for the production of such proteins. Their ability to properly configure and excrete proteins in functional form is an enormous advantage which should be contrasted with their inherent technological limitations. These cell systems exhibit a metabolic behaviour associated with elevated cell proliferation which involves a high consumption of glucose and glutamine, resulting in the rapid depletion of these nutrients in the medium and the accumulation of ammonium and lactate. Both phenomena contribute to the limitation of cell growth, the triggering of apoptotic processes and the loss of quality of the recombinant protein. Results: In this review, the use of alternative substrates and genetic modifications (host cell engineering) are analyzed as tools to overcome those limitations. In general, the results obtained are promising. However, metabolic and physiological phenomena involved in CHO cells are still barely understood. Thus, most of publications are focused on specific modifications rather than giving a systemic perspective. Conclusions: A deeper insight in the integrated understanding of metabolism and cell mechanisms is required in order to define complementary strategies at these two levels, so providing effective means to control nutrients consumption, reduce by-products and increase process productivity.
author	Altamirano,Claudia Berrios,Julio Vergara,Mauricio Becerra,Silvana
author_facet	Altamirano,Claudia Berrios,Julio Vergara,Mauricio Becerra,Silvana
author_sort	Altamirano,Claudia
title	Advances in improving mammalian cells metabolism for recombinant protein production
title_short	Advances in improving mammalian cells metabolism for recombinant protein production
title_full	Advances in improving mammalian cells metabolism for recombinant protein production
title_fullStr	Advances in improving mammalian cells metabolism for recombinant protein production
title_full_unstemmed	Advances in improving mammalian cells metabolism for recombinant protein production
title_sort	advances in improving mammalian cells metabolism for recombinant protein production
publisher	Pontificia Universidad Católica de Valparaíso
publishDate	2013
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-34582013000300010
work_keys_str_mv	AT altamiranoclaudia advancesinimprovingmammaliancellsmetabolismforrecombinantproteinproduction AT berriosjulio advancesinimprovingmammaliancellsmetabolismforrecombinantproteinproduction AT vergaramauricio advancesinimprovingmammaliancellsmetabolismforrecombinantproteinproduction AT becerrasilvana advancesinimprovingmammaliancellsmetabolismforrecombinantproteinproduction
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Advances in improving mammalian cells metabolism for recombinant protein production

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