Methylotrophic yeast hansenula polymorpha as production organism for recombinant pharmaceuticals

Since the onset of genetic engineering, yeasts belong to the preferred host cells for the production of heterologous proteins. They combine ease of genetic manipulation and cultivation with the ability to process and to modify the produced compounds according to a general eukaryotic scheme. Since yeasts do not contain pathogens, pyrogens or viral inclusions they constitute attractive production systems for proteins considered for therapeutic administration. At the beginning of gene technology the attention of biotechnologists focussed on the use of the best characterized species Saccharomyces cerevisiae. Insulin and hepatitis B vaccines are examples for S. cerevisiae-derived therapeutics. In recent years alternative yeast have become accessible for the techniques of modern molecular genetics and thus for potential applications in biotechnology. In this respect the methylotrophic yeast Hansenula polymorpha offers especially advantageous characteristics as host for the production of pharmaceutical proteins. As a consequence, production systems based on this yeast have been established for serum proteins, vaccines and other therapeutically important compounds. Some H. polymorpha-derived products are under preclinical or clinical trials at present and are expected to reach the market within the near future. In the following article the current status of this system is presented and discussed comparing it with other expression systems.