ArticleMicrobial cell factories2009
Altering the ribosomal subunit ratio in yeast maximizes recombinant protein yield.
Article in Microbial cell factories, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 63 citations in OpenAlex.
- Systematic perturbation of cultures of K. phaffii by carbon co-feeding show gene signatures associated with production of recombinant proteins.Microbial cell factories · 2026Article
- Spectral and Redox Properties of a Recombinant Mouse CytochromeMolecules (Basel, Switzerland) · 2023Article
- Heterologous (Over) Expression of Human SoLute Carrier (SLC) in Yeast: A Well-Recognized Tool for Human Transporter Function/Structure Studies.Life (Basel, Switzerland) · 2022Review
- Yeast Secretes High Amounts of Human Calreticulin without Cellular Stress.Current issues in molecular biology · 2022Article
- Chaperna: linking the ancient RNA and protein worlds.RNA biology · 2021Review
- Process development for the continuous production of heterologous proteins by the industrial yeast, Komagataella phaffii.Biotechnology and bioengineering · 2018Article
- Constitutively-stressed yeast strains are high-yielding for recombinant Fps1: implications for the translational regulation of an aquaporin.Microbial cell factories · 2017Article
- Ultra-deep sequencing of ribosome-associated poly-adenylated RNA in early Drosophila embryos reveals hundreds of conserved translated sORFs.DNA research : an international journal for rapid publication of reports on genes and genomes · 2016Article
- Comparative Proteome Analysis in Schizosaccharomyces pombe Identifies Metabolic Targets to Improve Protein Production and Secretion.Molecular & cellular proteomics : MCP · 2016Article
- Protein Folding Activity of the Ribosome is involved in Yeast Prion Propagation.Scientific reports · 2016Article
- Directed evolution of G protein-coupled receptors in yeast for higher functional production in eukaryotic expression hosts.Scientific reports · 2016Article
- Article
- G-protein coupled receptor solubilization and purification for biophysical analysis and functional studies, in the total absence of detergent.Bioscience reports · 2015Article
- Pichia pastoris regulates its gene-specific response to different carbon sources at the transcriptional, rather than the translational, level.BMC genomics · 2015Article
- Engineering the supply chain for protein production/secretion in yeasts and mammalian cells.Journal of industrial microbiology & biotechnology · 2015Review
- Playing catch-up with Escherichia coli: using yeast to increase success rates in recombinant protein production experiments.Frontiers in microbiology · 2014Article
- L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.PloS one · 2012Article
- Protein trafficking, ergosterol biosynthesis and membrane physics impact recombinant protein secretion in Pichia pastoris.Microbial cell factories · 2011Article
- Overexpression of human virus surface glycoprotein precursors induces cytosolic unfolded protein response in Saccharomyces cerevisiae.Microbial cell factories · 2011Article
- Overcoming barriers to membrane protein structure determination.Nature biotechnology · 2011Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe production of high yields of recombinant proteins is an enduring bottleneck in the post-genomic sciences that has yet to be addressed in a truly rational manner. Typically eukaryotic protein production experiments have relied on varying expression construct cassettes such as promoters and tags, or culture process parameters such as pH, temperature and aeration to enhance yields. These approaches require repeated rounds of trial-and-error optimization and cannot provide a mechanistic insight into the biology of recombinant protein production. We published an early transcriptome analysis that identified genes implicated in successful membrane protein production experiments in yeast. While there has been a subsequent explosion in such analyses in a range of production organisms, no one has yet exploited the genes identified. The aim of this study was to use the results of our previous comparative transcriptome analysis to engineer improved yeast strains and thereby gain an understanding of the mechanisms involved in high-yielding protein production hosts.
resultsWe show that tuning BMS1 transcript levels in a doxycycline-dependent manner resulted in optimized yields of functional membrane and soluble protein targets. Online flow microcalorimetry demonstrated that there had been a substantial metabolic change to cells cultured under high-yielding conditions, and in particular that high yielding cells were more metabolically efficient. Polysome profiling showed that the key molecular event contributing to this metabolically efficient, high-yielding phenotype is a perturbation of the ratio of 60S to 40S ribosomal subunits from approximately 1:1 to 2:1, and correspondingly of 25S:18S ratios from 2:1 to 3:1. This result is consistent with the role of the gene product of BMS1 in ribosome biogenesis.
conclusionThis work demonstrates the power of a rational approach to recombinant protein production by using the results of transcriptome analysis to engineer improved strains, thereby revealing the underlying biological events involved.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.