Sökning: WFRF:(Engqvist R) >
Different routes of...
Different routes of protein folding contribute to improved protein production in saccharomyces cerevisiae
-
- Li, Feiran, 1993 (författare)
- Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology
-
- Yu, R. (författare)
- Novo Nordisk Fonden,Novo Nordisk Foundation
-
- Engqvist, Martin, 1983 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
-
visa fler...
-
- Siewers, Verena, 1976 (författare)
- Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology
-
- Fuchs, Johannes (författare)
- Gothenburg University,Göteborgs universitet,Core Facilities, Proteomics,Core Facilities, Proteomics,University of Gothenburg
-
- Nielsen, Jens B, 1962 (författare)
- Danmarks Tekniske Universitet,Technical University of Denmark,Novo Nordisk Fonden,Novo Nordisk Foundation,BioInnovation Institute (BII),Chalmers tekniska högskola,Chalmers University of Technology
-
- Qi, Qi, 1992 (författare)
- Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology
-
visa färre...
-
(creator_code:org_t)
- 2020
- 2020
- Engelska.
-
Ingår i: mBio. - 2161-2129 .- 2150-7511. ; 11:6, s. 1-12
- Relaterad länk:
-
https://research.cha... (primary) (free)
-
visa fler...
-
https://gup.ub.gu.se...
-
https://doi.org/10.1...
-
https://research.cha...
-
visa färre...
Abstract
Ämnesord
Stäng
- Protein folding is often considered the flux controlling process in protein synthesis and secretion. Here, two previously isolated Saccharomyces cerevisiae strains with increased α-amylase productivity were analyzed in chemostat cultures at different dilution rates using multi-omics data. Based on the analysis, we identified different routes of the protein folding pathway to improve protein production. In the first strain, the increased abundance of proteins working on the folding process, coordinated with upregulated glycogen metabolism and trehalose metabolism, helped increase α-amylase productivity 1.95-fold compared to the level in the original strain in chemostat culture at a dilution rate of 0.2/h. The second strain further strengthened the folding precision to improve protein production. More precise folding helps the cell improve protein production efficiency and reduce the expenditure of energy on the handling of misfolded proteins. As calculated using an enzyme-constrained genome-scale metabolic model, the second strain had an increased productivity of 2.36-fold with lower energy expenditure than that of the original under the same condition. Further study revealed that the regulation of N-glycans played an important role in the folding precision control and that overexpression of the glucosidase Cwh41p can significantly improve protein production, especially for the strains with improved folding ca-pacity but lower folding precision. Our findings elucidated in detail the mechanisms in two strains having improved protein productivity and thereby provided novel insights for industrial recombinant protein production as well as demonstrating how multi-omics analysis can be used for identification of novel strain-engineering targets. IMPORTANCE Protein folding plays an important role in protein maturation and se-cretion. In recombinant protein production, many studies have focused on the folding pathway to improve productivity. Here, we identified two different routes for improving protein production by yeast. We found that improving folding precision is a better strategy. Dysfunction of this process is also associated with several aberrant protein-associated human diseases. Here, our findings about the role of glucosidase Cwh41p in the precision control system and the characterization of the strain with a more precise folding process could contribute to the development of novel therapeutic strategies. © 2020 Qi et al.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- Constraint-based modeling
- Multi-omics analysis
- Protein folding precision
- Protein production
- Protein secretory pathway
- amylase
- Cwh41 protein
- glucosidase
- glycan
- recombinant protein
- unclassified drug
- Article
- control system
- controlled study
- energy expenditure
- glycogen metabolism
- metabolomics
- multiomics
- nonhuman
- priority journal
- protein folding
- protein glycosylation
- protein modification
- protein secretion
- protein synthesis
- proteomics
- Saccharomyces cerevisiae
- strain difference
- transcriptomics
- Multi-omics analysis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
-
mBio
(Sök värdpublikationen i LIBRIS)
Till lärosätets databas
- Av författaren/redakt...
-
Li, Feiran, 1993
-
Yu, R.
-
Engqvist, Martin ...
-
Siewers, Verena, ...
-
Fuchs, Johannes
-
Nielsen, Jens B, ...
-
visa fler...
-
Qi, Qi, 1992
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinska och f ...
-
och Cell och molekyl ...
-
- NATURVETENSKAP
-
NATURVETENSKAP
-
och Biologi
-
och Biokemi och mole ...
-
- NATURVETENSKAP
-
NATURVETENSKAP
-
och Biologi
-
och Mikrobiologi
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinsk biotek ...
-
och Medicinsk biotek ...
- Artiklar i publikationen
-
mBio
- Av lärosätet
-
Göteborgs universitet
-
Chalmers tekniska högskola