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Engineering the pro...
Engineering the protein secretory pathway of Saccharomyces cerevisiae enables improved protein production
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- Huang, Mingtao, 1984 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Wang, Guokun, 1988 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Qin, Jiufu, 1985 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology,Danmarks Tekniske Universitet,Technical University of Denmark
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- Petranovic Nielsen, Dina, 1975 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Nielsen, Jens B, 1962 (författare)
- Danmarks Tekniske Universitet,Technical University of Denmark,Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- 2018-11-05
- 2018
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:47, s. E11025-E11032
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https://www.pnas.org...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Baker’s yeast Saccharomyces cerevisiae is one of the most important and widely used cell factories for recombinant protein production. Many strategies have been applied to engineer this yeast for improving its protein production capacity, but productivity is still relatively low, and with increasing market demand, it is important to identify new gene targets, especially targets that have synergistic effects with previously identified targets. Despite improved protein production, previous studies rarely focused on processes associated with intracellular protein retention. Here we identified genetic modifications involved in the secretory and trafficking pathways, the histone deacetylase complex, and carbohydrate metabolic processes as targets for improving protein secretion in yeast. Especially modifications on the endosome-to-Golgi trafficking was found to effectively reduce protein retention besides increasing protein secretion. Through combinatorial genetic manipulations of several of the newly identified gene targets, we enhanced the protein production capacity of yeast by more than fivefold, and the best engineered strains could produce 2.5 g/L of a fungal α-amylase with less than 10% of the recombinant protein retained within the cells, using fed-batch cultivation.
Ämnesord
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Bioprocessteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Bioprocess Technology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Annan industriell bioteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Other Industrial Biotechnology (hsv//eng)
Nyckelord
- Protein secretion
- Cell engineering
- Endosome-to-Golgi trafficking
- Intracellular
- Yeast cell factories
- Protein retention
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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