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 proce ss and to modify the produced compounds according to a general eukaryo tic scheme. Since yeasts do not contain pathogens, pyrogens or viral i nclusions they constitute attractive production systems for proteins c onsidered for therapeutic administration. At the beginning of gene tec hnology the attention of biotechnologists focussed on the use of the b est characterized species Saccharomyces cerevisiae. Insulin and hepati tis B vaccines are examples for S. cerevisiae-derived therapeutics. In recent years alternative yeast have become accessible for the techniq ues of modern molecular genetics and thus for potential applications i n biotechnology. In this respect the methylotrophic yeast Hansenula po lymorpha offers especially advantageous characteristics as host for th e 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. polymo rpha-derived products are under preclinical or clinical trials at pres ent and are expected to reach the market within the near future. In th e following article the current status of this system is presented and discussed comparing it with other expression systems.