Yeasts In Biotechnology

To date, S. cerevisiae and E. coli are the two microbial workhorses for commercialization of recombinant heterologous proteins. This is a direct reflection of the familiarity of molecular biologists with these two hosts, combined with the deep knowledge about their genetics, biochemistry, physiology, and fermentation technologies. Despite the significantly lower production costs of heterologous proteins using microbial cells compared to mammalian cells, the number of approved recombinant biopharmaceuticals from E. coli/S. cerevisiae and mammalian host systems increases over the years with the same rate (Ferrer-Miralles et al., 2009). • Likewise, S. cerevisiae and E. coli are also the predominant hosts used for industrial metabolite production (Porro et al., 2011). Metabolites commercially produced are generally released in the culture medium. Many more heterologous metabolites are commercially produced in S. cerevisiae than in E. coli; this fact mainly relates to a better cellular robustness against (i) adverse fermentation conditions and (ii) high concentration of the final compound offered by the eukaryotic host system. Indeed, even though many different heterologous metabolites have been obtained in E. coli, only a few went onto the market, because optimal yield and/or production and/or productivity have not been achieved. New nonconventional yeasts are also emerging on the biotech pipeline. Among these, P. pastoris and Kluyveromyces marxianus should be cited for the advanced studies carried out in many respect of basic and applied research. • Of course the perfect production host does not exist, yet. The tremendous power of recombinant DNA technology led to the development of the synthetic biology platform (Jarboe et al., 2010). • What will come out of all this? The ideal would be a laboratory-created biological system capable of replication and evolution, fed only by simple carbon and energy sources. In this case, it would be possible to (i) combine multiple foreign pathways in a single chassis for the production of diverse proteins and metabolites, (ii) design efficient de novo pathways, and (iii) engineer tolerance to adverse conditions and/or inhibitory compounds, at the same time looking to high quality and quantity standards, and high yield and productivity. The chemical synthesis, assembly, and cloning of a bacterial genome in the model yeast S. cerevisiae has been already described (Gibson et al., 2008; Lartigue et al., 2009; Benders et al., 2010). However, for the time being, since we are still far from understanding the secret of life, manipulation of natural or recombinant properties is still the quickest path to reach the goal. Whatever way, natural selection remains the most powerful tool to achieve the desired yeast cell factory. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA.