The methylotrophic yeast Hansenula polymorpha: its use in fundamental research and as a cell factory.

During the last decade methylotrophic yeasts have gained increasing interest, both for fundamental (van der Klei and Veenhuis, 1996) and applied purposes (van Dijk et al., 2000; Gellissen, 2000). The special value of these yeasts (mainly Pichia pastoris and Hansenula polymorpha) in fundamental research is undoubtedly related to studies on the principles of peroxisome homeostasis (biogenesis vs. degradation). In particular, the morphological features of peroxisome development and selective degradation are more strongly pronounced than in Saccharomyces cerevisiae, which makes it possible to induce and follow the details in mutants more easily. In addition, peroxisome induction in baker's yeast is restricted to growth on oleate (and thus b-oxidation), whereas in the methylotrophic yeasts various peroxisomal metabolic pathways may occur, depending on the composition of the growth medium. These organisms also display the strongest induction rates that may rise to a level at which up to 80% of the total cell volume is occupied by peroxisomes. The extremely high expression rates necessary to achieve this drew the attention of biotechnologists, who studied the use of these organisms as host for the production of valuable, heterologous proteins. Initially, P. pastoris was predominantly used; now H. polymorpha is gaining more and more attention. The H. polymorpha system was shown to provide a remarkably versatile technology platform for heterologous gene expression. The Hansenula toolbox now includes a variety of host strains, new integration sites and several novel strong promoters beyond those derived from methanol metabolism genes. In the ®rst H. polymorpha worldwide network (HPWN) conference, the recent developments in the use of this organism were discussed in a lively fashion. This report highlights several superb presentations of important, interesting and novel research.