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What makes Komagataella phaffii non-conventional?

  • Ata, Özge1, 2
  • Ergün, Burcu Gündüz3, 4
  • Fickers, Patrick5
  • Heistinger, Lina1, 2, 6
  • Mattanovich, Diethard1, 2
  • Rebnegger, Corinna1, 2, 7
  • Gasser, Brigitte1, 2, 4
  • 1 Institute of Microbiology and Microbial Biotechnology, Department of Biotechnology, University of Natural Resources and Life Sciences Vienna (BOKU), Austria. , (Austria)
  • 2 Austrian Centre of Biotechnology (ACIB), Vienna, Austria. , (Austria)
  • 3 UNAM-National Nanotechnology Research Center, Bilkent University, Ankara, Turkey. , (Turkey)
  • 4 Biotechnology Research Center, Ministry of Agriculture and Forestry, Ankara, Turkey. , (Turkey)
  • 5 Université de Liège - Gembloux Agro-Bio Tech, TERRA Teaching and Research Centre, Gembloux, Belgium. , (Belgium)
  • 6 Christian Doppler Laboratory for Innovative Immunotherapeutics, BOKU University of Natural Resources and Life Sciences Vienna, Austria. , (Austria)
  • 7 Christian Doppler Laboratory for growth-decoupled protein production in yeast, University of Natural Resources and Life Sciences Vienna (BOKU), Austria. , (Austria)
Published Article
FEMS Yeast Research
Oxford University Press
Publication Date
Nov 25, 2021
DOI: 10.1093/femsyr/foab059
PMID: 34849756


The important industrial protein production host Komagataella phaffii (syn Pichia pastoris) is classified as a non-conventional yeast. But what exactly makes K. phaffii non-conventional? In this review we set out to address the main differences to the 'conventional' yeast Saccharomyces cerevisiae, but also pinpoint differences to other non-conventional yeasts used in biotechnology. Apart from its methylotrophic lifestyle, K. phaffii is a Crabtree-negative yeast species. But even within the methylotrophs, K. phaffii possesses distinct regulatory features such as glycerol-repression of the methanol-utilization pathway or the lack of nitrate assimilation. Rewiring of the transcriptional networks regulating carbon (and nitrogen) source utilization clearly contributes to our understanding of genetic events occurring during evolution of yeast species. The mechanisms of mating-type switching and the triggers of morphogenic phenotypes represent further examples for how K. phaffii is distinguished from the model yeast S. cerevisiae. With respect to heterologous protein production, K. phaffii features high secretory capacity but secretes only low amounts of endogenous proteins. Different to S. cerevisiae, the Golgi apparatus of K. phaffii is stacked like in mammals. While it is tempting to speculate that Golgi architecture is correlated to the high secretion levels or the different N-glycan structures observed in K. phaffii, there is recent evidence against this. We conclude that K. phaffii is a yeast with unique features that has a lot of potential to explore both fundamental research questions and industrial applications. © The Author(s) 2021. Published by Oxford University Press on behalf of FEMS.

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