Increment de la producció de biomassa en bioreactors aplicant anàlisis metabòlics i eines enginyerils

• Autores: Pere Comas Sanchez
• Directores de la Tesis: Iván Martínez Monge (dir. tes.), Antoni Casablancas Mira (codir. tes.), Jordi Joan Cairó Badillo (codir. tes.)
• Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2020
• Idioma: español
• Tribunal Calificador de la Tesis: Francesc Gòdia Casablancas (presid.), Javier Macía Santamaría (secret.), Igor Bartolomé Marín de Mas (voc.)
• Programa de doctorado: Programa de Doctorado en Biotecnología por la Universidad Autónoma de Barcelona
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • The thesis presented is focused on improving the production of biopharmaceuticals products expressed in bacteria, yeast, and animal cells. The aim of the thesis is to improve bioprocess productivity of bacteria, yeast, and animal cell cultures through Bioprocess Engineering and Systems Biology. The work developed has a great interest in the field of Biotechnology, as about 60-70% of all biopharmaceuticals, including monoclonal antibodies, viral vaccines, and gene therapy vectors are produced in mammalian cells at present.

    The metabolism of two bacteria (E.coli M15 and E.coli BL21), two yeast (S. cerevisiae and P. pastoris), and two animal cell lines (hybridoma and HEK293) have been characterized using genome-scale metabolic models to understand the conversion of glucose to acetate (in case of E.coli), to ethanol (in case of S. cerevisiae and P. pastoris) and lactate ( in the case of hybridoma and HEK293). All the knowledge gained in the metabolic study has been applied to develop a robust monitoring and controlling tool to increase the culture volumetric productivity.

    On this basis, the metabolic data obtained in the previous studies are used in order to design culture strategies, mainly, fed-batch and perfusion depending on the microorganism used. Several tools are developed based on monitoring the biomass profile in order to calculate the feeding profile required for optimal growth. Two kinds of feeding profiles are designed in relation to biomass-related variables and non-biomass ones. In order to complete the work, a study where the application of the feeding profiles developed in bacteria, yeast, and animal cells is carried out in order to define the optimal feeding profile considering the culture requirements. In addition, the most suited strategy regarding the adaptation to the culture requirements is tested in an induction fed-batch with E.coli.