WFRF:(Ji Boyang 1983)
Sökning: WFRF:(Ji Boyang 1983) > Suppressors of amyl...
- 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 ...
- Elsevier BV,2022
Nummerbeteckningar
- LIBRIS-ID:oai:gup.ub.gu.se/320779
- https://gup.ub.gu.se/publication/320779URI
- https://doi.org/10.1016/j.ymben.2022.04.005DOI
- https://research.chalmers.se/publication/530318URI
Kompletterande språkuppgifter
- Språk:engelska
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Anmärkningar
- 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
- 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
- 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
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Li, Xiaowei,1986Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)lixiaow (författare)
- Ji, Boyang,1983BioInnovation Institute (BII),Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)boyang (författare)
- Wang, Yanyan,1989Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)yanyanw (författare)
- Ishchuk, Olena,1980Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)ishchuk (författare)
- Vorontsov, Egor,1988Gothenburg University,Göteborgs universitet,Core Facilities, Proteomics,Core Facilities, Proteomics,University of Gothenburg(Swepub:gu)xvoreg (författare)
- Petranovic Nielsen, Dina,1975Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation(Swepub:cth)dinap (författare)
- Siewers, Verena,1976Chalmers tekniska högskola,Chalmers University of Technology,Novo Nordisk Fonden,Novo Nordisk Foundation(Swepub:cth)siewers (författare)
- Engqvist, Martin,1983Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)marengq (författare)
- Chalmers tekniska högskolaNovo Nordisk Fonden (creator_code:org_t)
Sammanhörande titlar
- Ingår i:Metabolic Engineering: Elsevier BV72, s. 311-3241096-71761096-7184
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