title: Metabolic profiling of insect cell lines: Unveiling cell line determinants behind system's productivity.
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.
authors.affiliation: Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal; Instituto de Tecnologia Quimica e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Francisca
authors.initials: F
authors.lastname: Monteiro
authors.forename: Vicente
authors.initials: V
authors.lastname: Bernal
authors.forename: Xavier
authors.initials: X
authors.lastname: Saelens
authors.forename: Ana B
authors.initials: AB
authors.lastname: Lozano
authors.forename: Cristina
authors.initials: C
authors.lastname: Bernal
authors.forename: Angel
authors.initials: A
authors.lastname: Sevilla
authors.forename: Manuel J T
authors.initials: MJ
authors.lastname: Carrondo
authors.forename: Paula M
authors.initials: PM
authors.lastname: Alves
mesh_terms: D000818:Animals; D001709:Biotechnology; D002460:Cell Line; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis; D011994:Recombinant Proteins / Q000032:analysis / Q000378:metabolism*; D018411:Spodoptera / Q000166:cytology*
chemical_list: D011994:Recombinant Proteins
keywords: Baculovirus expression vector system; metabolic pathway analysis; metabolomics; recombinant protein production; virus-host interactions