ArticleMicrobial cell factories2020
Designing next generation recombinant protein expression platforms by modulating the cellular stress response in Escherichia coli.
Article in Microbial cell factories, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- A novel stationary phase approach for improved recombinant protein expression in Escherichia coli: beyond the exponential phase.Microbial cell factories · 2026Article
- Designing an optimized strategy for extracellular expression of recombinant human TNF-α inFrontiers in bioengineering and biotechnology · 2026Article
- Identification and analysis of the key genes for Escherichia coli heterologous protein expression by transcriptomic profiling.Molecular biology reports · 2024Article
- Identification of Key Genes during CaApplied and environmental microbiology · 2022Article
- CRISPRactivation-SMS, a message for PAM sequence independent gene up-regulation in Escherichia coli.Nucleic acids research · 2022Article
- Strategies for efficient production of recombinant proteins in Escherichia coli: alleviating the host burden and enhancing protein activity.Microbial cell factories · 2022Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundA cellular stress response (CSR) is triggered upon recombinant protein synthesis which acts as a global feedback regulator of protein expression. To remove this key regulatory bottleneck, we had previously proposed that genes that are up-regulated post induction could be part of the signaling pathways which activate the CSR. Knocking out some of these genes which were non-essential and belonged to the bottom of the E. coli regulatory network had provided higher expression of GFP and L-asparaginase.
resultsWe chose the best performing double knockout E. coli BW25113ΔelaAΔcysW and demonstrated its ability to enhance the expression of the toxic Rubella E1 glycoprotein by 2.5-fold by tagging it with sfGFP at the C-terminal end to better quantify expression levels. Transcriptomic analysis of this hyper-expressing mutant showed that a significantly lower proportion of genes got down-regulated post induction, which included genes for transcription, translation, protein folding and sorting, ribosome biogenesis, carbon metabolism, amino acid and ATP synthesis. This down-regulation which is a typical feature of the CSR was clearly blocked in the double knockout strain leading to its enhanced expression capability. Finally, we supplemented the expression of substrate uptake genes glpK and glpD whose down-regulation was not prevented in the double knockout, thus ameliorating almost all the negative effects of the CSR and obtained a further doubling in recombinant protein yields.
conclusionThe study validated the hypothesis that these up-regulated genes act as signaling messengers which activate the CSR and thus, despite having no casual connection with recombinant protein synthesis, can improve cellular health and protein expression capabilities. Combining gene knockouts with supplementing the expression of key down-regulated genes can counter the harmful effects of CSR and help in the design of a truly superior host platform for recombinant protein expression.
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