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Metabolic profiling of insect cell lines: Unveiling cell line determinants behind system's productivity

Authors

  • Francisca Monteiro,

    1. Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal
    2. Instituto de Tecnologia Quimica e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal
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  • Vicente Bernal,

    1. Departamento de Bioquímica y Biología Molecular B e Inmunología, Facultad de Química, Universidad de Murcia, Murcia, Spain
    Current affiliation:
    1. Grupo de Bioenergía. Dirección de Tecnología, Centro de Tecnología de REPSOL, Móstoles-Madrid, Spain
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  • Xavier Saelens,

    1. Department for Molecular Biomedical Research, VIB, Ghent, Belgium
    2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
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  • Ana B. Lozano,

    1. Departamento de Bioquímica y Biología Molecular B e Inmunología, Facultad de Química, Universidad de Murcia, Murcia, Spain
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  • Cristina Bernal,

    1. Departamento de Bioquímica y Biología Molecular B e Inmunología, Facultad de Química, Universidad de Murcia, Murcia, Spain
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  • Angel Sevilla,

    1. Departamento de Bioquímica y Biología Molecular B e Inmunología, Facultad de Química, Universidad de Murcia, Murcia, Spain
    2. Inbionova Biotech S.L., Universidad de Murcia, Murcia, Spain
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  • Manuel J.T. Carrondo,

    1. Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal
    2. Instituto de Tecnologia Quimica e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal
    3. Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal
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  • Paula M. Alves

    Corresponding author
    1. Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal
    2. Instituto de Tecnologia Quimica e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal
    • Correspondence to: P.M. Alves

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ABSTRACT

Baculovirus infection boosts the host biosynthetic activity towards the production of viral components and the recombinant protein of interest, hyper-productive phenotypes being the result of a successful adaptation of the cellular network to that scenario. Spodoptera frugiperda derived Sf9 and Trichoplusia ni derived High Five cell lines have a major track record for the production of recombinant proteins, with High Five cells presenting higher productivities. A metabolic profiling of the two insect cell lines was pursued to underpin specific cellular traits behind productive phenotypes. Multivariate analysis identified cell-line dependent metabolic signatures linked to productivity. Pathway analysis highlighted cellular pathways of paramount importance in supporting infection and protein production. Moreover, better producer phenotypes proved to be correlated with the capacity of cells to shift their metabolism in favor of energy-generating pathways to fuel biosynthesis, a scenario observed in the High Five cell line. Metabolomic profiling allowed us to identify metabolic pathways involved in infection and recombinant protein production, which can be selected as targets for further improvement of the system. Biotechnol. Bioeng. 2014;111: 816–828. © 2013 Wiley Periodicals, Inc.

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