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Suppressors of amyl...
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Chen, Xin,1980Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation
(författare)
Suppressors of amyloid-β toxicity improve recombinant protein production in yeast by reducing oxidative stress and tuning cellular metabolism
- Artikel/kapitelEngelska2022
Förlag, utgivningsår, omfång ...
Nummerbeteckningar
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LIBRIS-ID:oai:gup.ub.gu.se/320779
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https://gup.ub.gu.se/publication/320779URI
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https://doi.org/10.1016/j.ymben.2022.04.005DOI
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https://research.chalmers.se/publication/530318URI
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Li, Xiaowei,1986Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)lixiaow
(författare)
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Ji, Boyang,1983BioInnovation Institute (BII),Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)boyang
(författare)
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Wang, Yanyan,1989Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)yanyanw
(författare)
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Ishchuk, Olena,1980Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)ishchuk
(författare)
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Vorontsov, Egor,1988Gothenburg University,Göteborgs universitet,Core Facilities, Proteomics,Core Facilities, Proteomics,University of Gothenburg(Swepub:gu)xvoreg
(författare)
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Petranovic Nielsen, Dina,1975Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation(Swepub:cth)dinap
(författare)
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Siewers, Verena,1976Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation(Swepub:cth)siewers
(författare)
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Engqvist, Martin,1983Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)marengq
(författare)
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Chalmers tekniska högskolaNovo Nordisk Fonden
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Metabolic Engineering: Elsevier BV72, s. 311-3241096-71761096-7184
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Till lärosätets databas
- Av författaren/redakt...
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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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visa fler...
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Petranovic Niels ...
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Siewers, Verena, ...
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Engqvist, Martin ...
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Biokemi och mole ...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Cellbiologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinsk biotek ...
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och Medicinsk biotek ...
- Artiklar i publikationen
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Metabolic Engine ...
- Av lärosätet
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Göteborgs universitet
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Chalmers tekniska högskola