Sökning: onr:"swepub:oai:gup.ub.gu.se/302393" > Different routes of...
Fältnamn | Indikatorer | Metadata |
---|---|---|
000 | 06637naa a2200817 4500 | |
001 | oai:gup.ub.gu.se/302393 | |
003 | SwePub | |
008 | 240528s2020 | |||||||||||000 ||eng| | |
009 | oai:research.chalmers.se:4e367c4f-7925-479a-b961-e9f8da0d4985 | |
024 | 7 | a https://gup.ub.gu.se/publication/3023932 URI |
024 | 7 | a https://doi.org/10.1128/mBio.02743-202 DOI |
024 | 7 | a https://research.chalmers.se/publication/5203912 URI |
040 | a (SwePub)gud (SwePub)cth | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Li, Feiran,d 1993u Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology4 aut0 (Swepub:cth)feiranl |
245 | 1 0 | a Different routes of protein folding contribute to improved protein production in saccharomyces cerevisiae |
264 | 1 | c 2020 |
520 | a 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. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng |
650 | 7 | a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng |
650 | 7 | a NATURVETENSKAPx Biologix Mikrobiologi0 (SwePub)106062 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Biological Sciencesx Microbiology0 (SwePub)106062 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinsk bioteknologix Medicinsk bioteknologi0 (SwePub)304012 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Medical Biotechnologyx Medical Biotechnology0 (SwePub)304012 hsv//eng |
653 | a Constraint-based modeling | |
653 | a Multi-omics analysis | |
653 | a Protein folding precision | |
653 | a Protein production | |
653 | a Protein secretory pathway | |
653 | a amylase | |
653 | a Cwh41 protein | |
653 | a glucosidase | |
653 | a glycan | |
653 | a recombinant protein | |
653 | a unclassified drug | |
653 | a Article | |
653 | a control system | |
653 | a controlled study | |
653 | a energy expenditure | |
653 | a glycogen metabolism | |
653 | a metabolomics | |
653 | a multiomics | |
653 | a nonhuman | |
653 | a priority journal | |
653 | a protein folding | |
653 | a protein glycosylation | |
653 | a protein modification | |
653 | a protein secretion | |
653 | a protein synthesis | |
653 | a proteomics | |
653 | a Saccharomyces cerevisiae | |
653 | a strain difference | |
653 | a transcriptomics | |
653 | a Multi-omics analysis | |
700 | 1 | a Yu, R.u Novo Nordisk Fonden,Novo Nordisk Foundation4 aut |
700 | 1 | a Engqvist, Martin,d 1983u Chalmers tekniska högskola,Chalmers University of Technology4 aut0 (Swepub:cth)marengq |
700 | 1 | a Siewers, Verena,d 1976u Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology4 aut0 (Swepub:cth)siewers |
700 | 1 | a Fuchs, Johannesu Gothenburg University,Göteborgs universitet,Core Facilities, Proteomics,Core Facilities, Proteomics,University of Gothenburg4 aut0 (Swepub:gu)xfujoh |
700 | 1 | a Nielsen, Jens B,d 1962u Danmarks Tekniske Universitet,Technical University of Denmark,Novo Nordisk Fonden,Novo Nordisk Foundation,BioInnovation Institute (BII),Chalmers tekniska högskola,Chalmers University of Technology4 aut0 (Swepub:cth)nielsenj |
700 | 1 | a Qi, Qi,d 1992u Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology4 aut0 (Swepub:cth)fomde |
710 | 2 | a Novo Nordisk Fondenb Chalmers tekniska högskola4 org |
773 | 0 | t mBiog 11:6, s. 1-12q 11:6<1-12x 2161-2129x 2150-7511 |
856 | 4 | u https://research.chalmers.se/publication/520391/file/520391_Fulltext.pdfx primaryx freey FULLTEXT |
856 | 4 8 | u https://gup.ub.gu.se/publication/302393 |
856 | 4 8 | u https://doi.org/10.1128/mBio.02743-20 |
856 | 4 8 | u https://research.chalmers.se/publication/520391 |
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