Towards systems metabolic engineering in Pichia pastoris

Schwarzhans JP, Luttermann T, Geier M, Kalinowski J, Friehs K (2017)
BIOTECHNOLOGY ADVANCES 35(6): 681-710.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Abstract / Bemerkung
The methylotrophic yeast Pichia pastoris is firmly established as a host for the production of recombinant proteins, frequently outperforming other heterologous hosts. Already, a sizeable amount of systems biology knowledge has been acquired for this non-conventional yeast. By applying various omics-technologies, productivity features have been thoroughly analyzed and optimized via genetic engineering. However, challenging clonal variability, limited vector repertoire and insufficient genome annotation have hampered further developments. Yet, in the last few years a reinvigorated effort to establish P. pastoris as a host for both protein and metabolite production is visible. A variety of compounds from terpenoids to polyketides have been synthesized, often exceeding the productivity of other microbial systems. The clonal variability was systematically investigated and strategies formulated to circumvent untargeted events, thereby streamlining the screening procedure. Promoters with novel regulatory properties were discovered or engineered from existing ones. The genetic tractability was increased via the transfer of popular manipulation and assembly techniques, as well as the creation of new ones. A second generation of sequencing projects culminated in the creation of the second best functionally annotated yeast genome. In combination with landmark physiological insights and increased output of omics-data, a good basis for the creation of refined genome-scale metabolic models was created. The first application of model-based metabolic engineering in P. pastoris showcased the potential of this approach. Recent efforts to establish yeast peroxisomes for compartmentalized metabolite synthesis appear to fit ideally with the well-studied high capacity peroxisomal machinery of P. pastoris. Here, these recent developments are collected and reviewed with the aim of supporting the establishment of systems metabolic engineering in P. pastoris.
Stichworte
Pichia pastoris; Komagataella phaffii; Non-conventional yeasts; Genetic; engineering; Metabolic engineering; Recombinant protein production; Promoters; Systems biology; Physiology
Erscheinungsjahr
2017
Zeitschriftentitel
BIOTECHNOLOGY ADVANCES
Band
35
Ausgabe
6
Seite(n)
681-710
ISSN
0734-9750
eISSN
1873-1899
Page URI
https://pub.uni-bielefeld.de/record/2916444

Zitieren

Schwarzhans JP, Luttermann T, Geier M, Kalinowski J, Friehs K. Towards systems metabolic engineering in Pichia pastoris. BIOTECHNOLOGY ADVANCES. 2017;35(6):681-710.
Schwarzhans, J. P., Luttermann, T., Geier, M., Kalinowski, J., & Friehs, K. (2017). Towards systems metabolic engineering in Pichia pastoris. BIOTECHNOLOGY ADVANCES, 35(6), 681-710. doi:10.1016/j.biotechadv.2017.07.009
Schwarzhans, J. P., Luttermann, T., Geier, M., Kalinowski, J., and Friehs, K. (2017). Towards systems metabolic engineering in Pichia pastoris. BIOTECHNOLOGY ADVANCES 35, 681-710.
Schwarzhans, J.P., et al., 2017. Towards systems metabolic engineering in Pichia pastoris. BIOTECHNOLOGY ADVANCES, 35(6), p 681-710.
J.P. Schwarzhans, et al., “Towards systems metabolic engineering in Pichia pastoris”, BIOTECHNOLOGY ADVANCES, vol. 35, 2017, pp. 681-710.
Schwarzhans, J.P., Luttermann, T., Geier, M., Kalinowski, J., Friehs, K.: Towards systems metabolic engineering in Pichia pastoris. BIOTECHNOLOGY ADVANCES. 35, 681-710 (2017).
Schwarzhans, Jan Philipp, Luttermann, Tobias, Geier, Martina, Kalinowski, Jörn, and Friehs, Karl. “Towards systems metabolic engineering in Pichia pastoris”. BIOTECHNOLOGY ADVANCES 35.6 (2017): 681-710.

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