Sistema integrat de producció de proteïnes heteròlogues en el llevat metilotròfic\i (Pichia Pastoris) \i0 per a l'obtenció de productes d'interès farmacèutic i veterinari

The global objective of teh project is the development, using a multidisciplinary approach, of an integrated system for the production of heterologous proteins in the yeast Pichia pastoris for their high added value applications in the pharmaceutical and veterinary industry, as well as in medical research. In this project, three classes of proteins will be produced: 1)microbial lipases from fungi and yeast, namely from Rhizopus oryzae and Candida rugosa, for the resolution of racemic mixtures in chemical reactions of interest for the pharmaceutical industry. 2)The equine Chorionic Gonadotropin (eCG) a hormone belonging to the gonadotropines family of hormones, which has the function in equines to mimic the FSH (Follicle stimulating Hormone), stimulating the production of strogens and progesterone during pregnancy of mares. 3)A human protein complex related with brain function and the ethiology of neurodegenerative diseases. The produced heterologous proteins will be compared with their native counterparts (with the exection of the brain complexes) with the aim to assess the potential (in terms of quality) of the P. pastoris expression system to express these classes of proteins. In order to achieve the global objective, several aspects will be integrated to llow a better understanding of the global production system. As well as to provide tools and methodologies for its engineering, from the gene to the pilot plant. This will include genetic, physiological and metabolic aspects, fermentation strategies developmet, monitoring, modelling and control of the fermentation processes, and up (60 litres) and down scaling. Also, it will consider several applied aspects of the produced proteins, aiming at their industrial use (lipades and eCG) or use in basic studies (brain protein complexes). Overall, this integrated approach has the ultimate goal to provide to the industry with an optimised and controlled fermentation technology that assures maximum product