Yeasts as a Tool for Heterologous Gene Expression

The yeasts Saccharomyces cerevisiae and Pichia pastoris are attractive hosts for production of human proteins. The main advantages offered by these systems are the well-developed and easily accessible genetic tools, rapid growth, the simple and inexpensive culture media, and many of the cellular and metabolic processes found in higher eukaryotes are conserved in both yeast species. In this chapter, we describe the production of two proteins of therapeutic interest: the human P53 tumor suppressor and the viral HBsAg in P. pastoris and S. cerevisiae using the strong and inducible promoters AOX1 and Gal10/Cyc1, respectively. Besides the production as a goal of both expressions, we also report on an unexpected result that has occurred in S. cerevisiae : The overexpression of human p53 induces yeast cell death with characteristic markers of apoptosis, such as the externalization of phosphatidylserines and DNA strand cleavage.