Keynote Lecture : Introduction to Pichia
The Pichia pastoris expression system is the product of the efforts of many researchers over more than 35 years. The major characteristics of the system reflect a combination of planned development and serendipity. The organism was initially selected as a source of single-cell protein, yeast biomass utilized as a high-protein animal feed. Although this effort did not result in a commercially viable process, the superior growth characteristics of P. pastoris recognized by early researchers along with the development of high-density culture media and methods directly translated to the expression system. A second major characteristic, the alcohol oxidase (AOX1) gene promoter system, is a consequence of the ability of this yeast to grow on methanol and its need for huge quantities of AOX1 gene product when grown on this substrate. Yet a third characteristic of P. pastoris is its molecular genetic similarity to Saccharomyces cerevisiae, allowing researchers to adapt many procedures already in place for this well-studied yeast. However, not all features are similar between these yeasts. One important difference is N-liked glycosylation, which tends to be relatively short chained in P. pastoris but can stretch for more than a hundred mannose residues per chain in S. cerevisiae.
P. pastoris expression science has continued to move forward. Two major areas of progress are the development of host strains that add human-like carbohydrate structures to proteins and the sequencing of the P. pastoris genome.