ArticlePLoS computational biology2021
Analysis of 11,430 recombinant protein production experiments reveals that protein yield is tunable by synonymous codon changes of translation initiation sites.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Global translational reprogramming inVirulence · 2026Article
- Genomic indicators of gene function: a systematic assessment of the human genome.G3 (Bethesda, Md.) · 2026Article
- Design of a multi-epitope Staphylococcus aureus vaccine integrating a protein A variant, α-hemolysin, and fibronectin-binding protein A through reverse vaccinology.Scientific reports · 2026Article
- Deciphering the determinants of recombinant protein expression across the human secretome.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mutability and hypermutation antagonize immunoglobulin codon optimality.Molecular cell · 2025Article
- GRACE: Generative Redesign in Artificial Computational Enzymology.ACS synthetic biology · 2024Article
- Article
- The use of RNA-based treatments in the field of cancer immunotherapy.Molecular cancer · 2023Review
- Gene recoding by synonymous mutations creates promiscuous intragenic transcription initiation in mycobacteria.bioRxiv : the preprint server for biology · 2023Article
- Influence of the mRNA initial region on protein production: a case study using recombinant detoxified pneumolysin as a model.Frontiers in bioengineering and biotechnology · 2023Article
- TISIGNER.com: web services for improving recombinant protein production.Nucleic acids research · 2021Article
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Authors and funding
6 authors.
Funding
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Abstract
Recombinant protein production is a key process in generating proteins of interest in the pharmaceutical industry and biomedical research. However, about 50% of recombinant proteins fail to be expressed in a variety of host cells. Here we show that the accessibility of translation initiation sites modelled using the mRNA base-unpairing across the Boltzmann's ensemble significantly outperforms alternative features. This approach accurately predicts the successes or failures of expression experiments, which utilised Escherichia coli cells to express 11,430 recombinant proteins from over 189 diverse species. On this basis, we develop TIsigner that uses simulated annealing to modify up to the first nine codons of mRNAs with synonymous substitutions. We show that accessibility captures the key propensity beyond the target region (initiation sites in this case), as a modest number of synonymous changes is sufficient to tune the recombinant protein expression levels. We build a stochastic simulation model and show that higher accessibility leads to higher protein production and slower cell growth, supporting the idea of protein cost, where cell growth is constrained by protein circuits during overexpression.
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