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Maria Luisa Tutino - One of the best experts on this subject based on the ideXlab platform.

  • process optimization for Recombinant Protein production in the psychrophilic bacterium pseudoalteromonas haloplanktis
    Process Biochemistry, 2011
    Co-Authors: Maria Giuliani, Ermenegilda Parrilli, Gennaro Marino, Pau Ferrer, Kristin Baumann, Maria Luisa Tutino
    Abstract:

    Abstract A new regulated expression system has been developed for Recombinant Protein production in Pseudoalteromonas haloplanktis , strongly induced by the presence of l -malate in culture medium. In optimized induction conditions, high yields of soluble Recombinant model Proteins were obtained in small scale expression experiments. However, performances of the new expression system are still not satisfactory for large scale Recombinant Protein production. To improve the psychrophilic expression system, the influence of medium composition and cultivation operational strategies on biomass concentration, growth rate and Protein production have been investigated in this study. A new defined medium, containing branched amino acids (L, I, V) as carbon sources, was developed resulting in over sevenfold increase of reporter enzyme production and threefold of biomass yield with respect to the previously optimized conditions. The new synthetic medium was also tested for the production of a Recombinant antibody fragment. In batch cultivation, up to 0.9 mg g dry cell weight −1 of soluble 3H6 Fab were recovered in bacterial periplasm. Moreover, the new optimized medium was tested for P. haloplanktis chemostat cultivation. A continuous process for 3H6 Fab production was developed leading to a volumetric productivity of about 0.2 mg L −1  h −1 of soluble and periplasmic Recombinant antibody.

  • a novel genetic system for Recombinant Protein secretion in the antarctic pseudoalteromonas haloplanktis tac125
    Microbial Cell Factories, 2006
    Co-Authors: Angela Maria Cusano, Ermenegilda Parrilli, Gennaro Marino, Maria Luisa Tutino
    Abstract:

    Background The final aim of Recombinant Protein production is both to have a high specific production rate and a high product quality. It was already shown that using cold-adapted bacteria as host vectors, some "intractable" Proteins can be efficiently produced at temperature as low as 4°C.

Joseph Shiloach - One of the best experts on this subject based on the ideXlab platform.

  • knocking out ornithine decarboxylase antizyme 1 oaz1 improves Recombinant Protein expression in the hek293 cell line
    Medical Sciences, 2018
    Co-Authors: Laura Abaandou, Joseph Shiloach
    Abstract:

    Creating efficient cell lines is a priority for the biopharmaceutical industry, which produces biologicals for various uses. A recent approach to achieving this goal is the use of non-coding RNAs, microRNA (miRNA) and small interfering RNA (siRNA), to identify key genes that can potentially improve production or growth. The ornithine decarboxylase antizyme 1 (OAZ1) gene, a negative regulator of polyamine biosynthesis, was identified in a genome-wide siRNA screen as a potential engineering target, because its knock down by siRNA increased Recombinant Protein expression from human embryonic kidney 293 (HEK293) cells by two-fold. To investigate this further, the OAZ1 gene in HEK293 cells was knocked out using CRISPR genome editing. The OAZ1 knockout cell lines displayed up to four-fold higher expression of both stably and transiently expressed Proteins, with comparable growth and metabolic activity to the parental cell line; and an approximately three-fold increase in intracellular polyamine content. The results indicate that genetic inactivation of OAZ1 in HEK293 cells is an effective strategy to improve Recombinant Protein expression in HEK293 cells.

  • knocking out ornithine decarboxylase antizyme 1 oaz1 improves Recombinant Protein expression in the hek293 cell line
    Medical Sciences, 2018
    Co-Authors: Laura Abaandou, Joseph Shiloach
    Abstract:

    Creating efficient cell lines is a priority for the biopharmaceutical industry, which produces biologicals for various uses. A recent approach to achieving this goal is the use of non-coding RNAs, microRNA (miRNA) and small interfering RNA (siRNA), to identify key genes that can potentially improve production or growth. The ornithine decarboxylase antizyme 1 (OAZ1) gene, a negative regulator of polyamine biosynthesis, was identified in a genome-wide siRNA screen as a potential engineering target, because its knock down by siRNA increased Recombinant Protein expression from human embryonic kidney 293 (HEK293) cells by two-fold. To investigate this further, the OAZ1 gene in HEK293 cells was knocked out using CRISPR genome editing. The OAZ1 knockout cell lines displayed up to four-fold higher expression of both stably and transiently expressed Proteins, with comparable growth and metabolic activity to the parental cell line; and an approximately three-fold increase in intracellular polyamine content. The results indicate that genetic inactivation of OAZ1 in HEK293 cells is an effective strategy to improve Recombinant Protein expression in HEK293 cells.

Mark C Smales - One of the best experts on this subject based on the ideXlab platform.

  • the cold shock response in cultured mammalian cells harnessing the response for the improvement of Recombinant Protein production
    Biotechnology and Bioengineering, 2006
    Co-Authors: Mohamed B Alfageeh, Rosalyn J Marchant, Martin J Carden, Mark C Smales
    Abstract:

    There are a growing number of reports on the sub-physiological temperature culturing (<37°C) of mammalian cells for increased Recombinant Protein yield, although the effect is variable between cell lines, expression systems, and the product of interest. What is becoming clear is that exposing mammalian cells to sub-physiological temperatures invokes a coordinated cellular response involving modulation of the cell cycle, metabolism, transcription, translation, and the cell cytoskeleton. Opportunities currently exist for further enhancement of the cold-shock effect on Recombinant Protein production in mammalian cells through advancements in our understanding of the mechanisms involved in the cold-shock response. © 2005 Wiley Periodicals, Inc.

  • the cold shock response in cultured mammalian cells harnessing the response for the improvement of Recombinant Protein production
    Biotechnology and Bioengineering, 2006
    Co-Authors: Mohamed B Alfageeh, Rosalyn J Marchant, Martin J Carden, Mark C Smales
    Abstract:

    There are a growing number of reports on the sub-physiological temperature culturing (<37 degrees C) of mammalian cells for increased Recombinant Protein yield, although the effect is variable between cell lines, expression systems, and the product of interest. What is becoming clear is that exposing mammalian cells to sub-physiological temperatures invokes a coordinated cellular response involving modulation of the cell cycle, metabolism, transcription, translation, and the cell cytoskeleton. Opportunities currently exist for further enhancement of the cold-shock effect on Recombinant Protein production in mammalian cells through advancements in our understanding of the mechanisms involved in the cold-shock response.

Florian M Wurm - One of the best experts on this subject based on the ideXlab platform.

Pau Ferrer - One of the best experts on this subject based on the ideXlab platform.

  • Protein trafficking ergosterol biosynthesis and membrane physics impact Recombinant Protein secretion in pichia pastoris
    Microbial Cell Factories, 2011
    Co-Authors: Kristin Baumann, Nuria Adelantado, Christine Lang, Diethard Mattanovich, Pau Ferrer
    Abstract:

    Background The increasing availability of 'omics' databases provide important platforms for yeast engineering strategies since they offer a lot of information on the physiology of the cells under diverse growth conditions, including environmental stresses. Notably, only a few of these approaches have considered a performance under Recombinant Protein production conditions. Recently, we have identified a beneficial effect of low oxygen availability on the expression of a human Fab fragment in Pichia pastoris. Transcriptional analysis and data mining allowed for the selection of potential targets for strain improvement. A first selection of these candidates has been evaluated as Recombinant Protein secretion enhancers.

  • process optimization for Recombinant Protein production in the psychrophilic bacterium pseudoalteromonas haloplanktis
    Process Biochemistry, 2011
    Co-Authors: Maria Giuliani, Ermenegilda Parrilli, Gennaro Marino, Pau Ferrer, Kristin Baumann, Maria Luisa Tutino
    Abstract:

    Abstract A new regulated expression system has been developed for Recombinant Protein production in Pseudoalteromonas haloplanktis , strongly induced by the presence of l -malate in culture medium. In optimized induction conditions, high yields of soluble Recombinant model Proteins were obtained in small scale expression experiments. However, performances of the new expression system are still not satisfactory for large scale Recombinant Protein production. To improve the psychrophilic expression system, the influence of medium composition and cultivation operational strategies on biomass concentration, growth rate and Protein production have been investigated in this study. A new defined medium, containing branched amino acids (L, I, V) as carbon sources, was developed resulting in over sevenfold increase of reporter enzyme production and threefold of biomass yield with respect to the previously optimized conditions. The new synthetic medium was also tested for the production of a Recombinant antibody fragment. In batch cultivation, up to 0.9 mg g dry cell weight −1 of soluble 3H6 Fab were recovered in bacterial periplasm. Moreover, the new optimized medium was tested for P. haloplanktis chemostat cultivation. A continuous process for 3H6 Fab production was developed leading to a volumetric productivity of about 0.2 mg L −1  h −1 of soluble and periplasmic Recombinant antibody.