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Suppressors of amyl...
Suppressors of amyloid-β toxicity improve recombinant protein production in yeast by reducing oxidative stress and tuning cellular metabolism
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- Chen, Xin, 1980 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation
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- Li, Xiaowei, 1986 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Ji, Boyang, 1983 (author)
- BioInnovation Institute (BII),Chalmers tekniska högskola,Chalmers University of Technology
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- Wang, Yanyan, 1989 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Ishchuk, Olena, 1980 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Vorontsov, Egor, 1988 (author)
- Gothenburg University,Göteborgs universitet,Core Facilities, Proteomics,Core Facilities, Proteomics,University of Gothenburg
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- Petranovic Nielsen, Dina, 1975 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation
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- Siewers, Verena, 1976 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation
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- Engqvist, Martin, 1983 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
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In: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 72, s. 311-324
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Abstract
Subject headings
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- High-level production of recombinant proteins in industrial microorganisms is often limited by the formation of misfolded proteins or protein aggregates, which consequently induce cellular stress responses. We hypothesized that in a yeast Alzheimer's disease (AD) model overexpression of amyloid-β peptides (Aβ42), one of the main peptides relevant for AD pathologies, induces similar phenotypes of cellular stress. Using this humanized AD model, we previously identified suppressors of Aβ42 cytotoxicity. Here we hypothesize that these suppressors could be used as metabolic engineering targets to alleviate cellular stress and improve recombinant protein production in the yeast Saccharomyces cerevisiae. Forty-six candidate genes were individually deleted and twenty were individually overexpressed. The positive targets that increased recombinant α-amylase production were further combined leading to an 18.7-fold increased recombinant protein production. These target genes are involved in multiple cellular networks including RNA processing, transcription, ER-mitochondrial complex, and protein unfolding. By using transcriptomics and proteomics analyses, combined with reverse metabolic engineering, we showed that reduced oxidative stress, increased membrane lipid biosynthesis and repressed arginine and sulfur amino acid biosynthesis are significant pathways for increased recombinant protein production. Our findings provide new insights towards developing synthetic yeast cell factories for biosynthesis of valuable proteins.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- Amyloid-β
- Cell engineering
- Cell stress
- Protein misfolding and aggregation
- Yeast cell factories
- Amino acids
- Biochemistry
- Biosynthesis
- Cytology
- Metabolic engineering
- Metabolism
- Neurodegenerative diseases
- Peptides
- Recombinant proteins
- Transcription
- Transcription factors
- Yeast
- Alzheimers disease
- Cellular stress
- Disease models
- Protein aggregation
- Protein misfolding
- Recombinant protein productions
- Yeast cell
- Yeast cell factory
- Glycoproteins
- amylase
- amyloid beta protein
- amyloid beta protein[1-42]
- arginine
- membrane lipid
- mitochondrial protein
- recombinant protein
- sulfur amino acid
- Article
- cell metabolism
- gene deletion
- gene expression
- gene overexpression
- genetic transcription
- lipogenesis
- mitochondrion
- nonhuman
- oxidative stress
- phenotype
- protein expression
- protein unfolding
- proteomics
- RNA processing
- Saccharomyces cerevisiae
- transcriptomics
- Protein misfolding and aggregation
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Chen, Xin, 1980
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Li, Xiaowei, 198 ...
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Ji, Boyang, 1983
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Wang, Yanyan, 19 ...
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Ishchuk, Olena, ...
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Vorontsov, Egor, ...
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show more...
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Petranovic Niels ...
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Siewers, Verena, ...
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Engqvist, Martin ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
- Articles in the publication
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Metabolic Engine ...
- By the university
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University of Gothenburg
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Chalmers University of Technology