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https://doi.org/10.21256/zhaw-29847| Publication type: | Article in scientific journal |
| Type of review: | Peer review (publication) |
| Title: | Engineering of the unfolded protein response pathway in Pichia pastoris : enhancing production of secreted recombinant proteins |
| Authors: | Raschmanová, Hana Weninger, Astrid Knejzlík, Zdeněk Melzoch, Karel Kovar, Karin |
| et. al: | No |
| DOI: | 10.1007/s00253-021-11336-5 10.21256/zhaw-29847 |
| Published in: | Applied Microbiology and Biotechnology |
| Volume(Issue): | 105 |
| Page(s): | 4397 |
| Pages to: | 4414 |
| Issue Date: | 26-May-2021 |
| Publisher / Ed. Institution: | Springer |
| ISSN: | 0175-7598 1432-0614 |
| Language: | English |
| Subjects: | Chaperone; Co-expression strategy; Folding and secretion; Pichia pastoris; Productivity of recombinant protein production; Unfolded protein response (UPR); Recombinant protein; Saccharomycetales; Fungal protein |
| Subject (DDC): | 579: Microbiology 660.6: Biotechnology |
| Abstract: | Folding and processing of proteins in the endoplasmic reticulum (ER) are major impediments in the production and secretion of proteins from Pichia pastoris (Komagataella sp.). Overexpression of recombinant genes can overwhelm the innate secretory machinery of the P. pastoris cell, and incorrectly folded proteins may accumulate inside the ER. To restore proper protein folding, the cell naturally triggers an unfolded protein response (UPR) pathway, which upregulates the expression of genes coding for chaperones and other folding-assisting proteins (e.g., Kar2p, Pdi1, Ero1p) via the transcription activator Hac1p. Unfolded/misfolded proteins that cannot be repaired are degraded via the ER-associated degradation (ERAD) pathway, which decreases productivity. Co-expression of selected UPR genes, along with the recombinant gene of interest, is a common approach to enhance the production of properly folded, secreted proteins. Such an approach, however, is not always successful and sometimes, protein productivity decreases because of an unbalanced UPR. This review summarizes successful chaperone co-expression strategies in P. pastoris that are specifically related to overproduction of foreign proteins and the UPR. In addition, it illustrates possible negative effects on the cell's physiology and productivity resulting from genetic engineering of the UPR pathway. We have focused on Pichia's potential for commercial production of valuable proteins and we aim to optimize molecular designs so that production strains can be tailored to suit a specific heterologous product. |
| Further description: | Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch) |
| URI: | https://digitalcollection.zhaw.ch/handle/11475/29847 |
| Fulltext version: | Published version |
| License (according to publishing contract): | CC BY 4.0: Attribution 4.0 International |
| Departement: | Life Sciences and Facility Management |
| Organisational Unit: | Institute of Chemistry and Biotechnology (ICBT) |
| Appears in collections: | Publikationen Life Sciences und Facility Management |
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|---|---|---|---|---|
| 2021_Raschmanova-etal_Engineering-unfolded-protein-response-Pichia-pastoris.pdf | 668.35 kB | Adobe PDF |  View/Open |
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Raschmanová, H., Weninger, A., Knejzlík, Z., Melzoch, K., & Kovar, K. (2021). Engineering of the unfolded protein response pathway in Pichia pastoris : enhancing production of secreted recombinant proteins. Applied Microbiology and Biotechnology, 105, 4397–4414. https://doi.org/10.1007/s00253-021-11336-5
Raschmanová, H. et al. (2021) ‘Engineering of the unfolded protein response pathway in Pichia pastoris : enhancing production of secreted recombinant proteins’, Applied Microbiology and Biotechnology, 105, pp. 4397–4414. Available at: https://doi.org/10.1007/s00253-021-11336-5.
H. Raschmanová, A. Weninger, Z. Knejzlík, K. Melzoch, and K. Kovar, “Engineering of the unfolded protein response pathway in Pichia pastoris : enhancing production of secreted recombinant proteins,” Applied Microbiology and Biotechnology, vol. 105, pp. 4397–4414, May 2021, doi: 10.1007/s00253-021-11336-5.
RASCHMANOVÁ, Hana, Astrid WENINGER, Zdeněk KNEJZLÍK, Karel MELZOCH und Karin KOVAR, 2021. Engineering of the unfolded protein response pathway in Pichia pastoris : enhancing production of secreted recombinant proteins. Applied Microbiology and Biotechnology. 26 Mai 2021. Bd. 105, S. 4397–4414. DOI 10.1007/s00253-021-11336-5
Raschmanová, Hana, Astrid Weninger, Zdeněk Knejzlík, Karel Melzoch, and Karin Kovar. 2021. “Engineering of the Unfolded Protein Response Pathway in Pichia Pastoris : Enhancing Production of Secreted Recombinant Proteins.” Applied Microbiology and Biotechnology 105 (May): 4397–4414. https://doi.org/10.1007/s00253-021-11336-5.
Raschmanová, Hana, et al. “Engineering of the Unfolded Protein Response Pathway in Pichia Pastoris : Enhancing Production of Secreted Recombinant Proteins.” Applied Microbiology and Biotechnology, vol. 105, May 2021, pp. 4397–414, https://doi.org/10.1007/s00253-021-11336-5.
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