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03287nam a2200565Ia 4500 |
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10.1016-j.ymben.2022.04.005 |
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220706s2022 CNT 000 0 und d |
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|a 10967176 (ISSN)
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|a Suppressors of amyloid-β toxicity improve recombinant protein production in yeast by reducing oxidative stress and tuning cellular metabolism
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|b Academic Press Inc.
|c 2022
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|z View Fulltext in Publisher
|u https://doi.org/10.1016/j.ymben.2022.04.005
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|a 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. © 2022 The Authors
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|a Alzheimers disease
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|a Amino acids
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|a Amyloid-β
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|a Amyloid-β
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|a Biochemistry
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|a Biosynthesis
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|a Cell engineering
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|a Cell stress
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|a Cell stress
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|a Cellular stress
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|a Cytology
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|a Disease models
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|a Glycoproteins
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|a Metabolic engineering
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|a Metabolism
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|a Neurodegenerative diseases
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|a Peptides
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|a Protein aggregation
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|a Protein misfolding
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|a Protein misfolding and aggregation
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|a Recombinant protein productions
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|a Recombinant proteins
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|a Transcription
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|a Transcription factors
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|a Yeast
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|a Yeast cell
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|a Yeast cell factories
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|a Yeast cell factory
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|a Chen, X.
|e author
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|a Engqvist, M.K.M.
|e author
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|a Ishchuk, O.P.
|e author
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|a Ji, B.
|e author
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|a Li, X.
|e author
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|a Petranovic, D.
|e author
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|a Siewers, V.
|e author
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|a Vorontsov, E.
|e author
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|a Wang, Y.
|e author
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|t Metabolic Engineering
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