Codon harmonization—Going beyond the speed limit for protein expression
Open accessAbstract
Codon usage distribution has been soundly used by nature to fine tune protein biogenesis. Alteration of the mRNA structure or sequential scheduling of codons can profoundly affect translation, thus altering protein yield, functionality, solubility, and proper folding. Building on these observations, here, we present an evaluation of different recently designed algorithms of sequence adaptation based on Codon Adaptation Index (CAI) profiling. The first algorithm globally harmonizes synonymous codons in the original sequence in full respect to the heterologous expression host codon usage. The second recodes the sequence in accordance with the native sequence CAI profile. Our data, generated on three model proteins, highlights the importance to consider gene recoding as a parameter itself for recombinant protein expression improvement.
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At the transcriptional level, codon harmonization has largely improved expression of antibody fragments.
“At the transcriptional level, the concept of “codon harmonization”, a sophisticated version of the codon usage optimization, has largely improved the expression of antibodies fragments [60,103].”
From Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments (2020) · cites this paper as [103]
In “Expression of CAI profile optimized sequences” (page unavailable), the paper reports that codon-optimized sequences markedly increased protein expression of scFv D1.3, an antibody fragment. It does not establish an improvement at the transcriptional level: the reported outcome is protein abundance, and the paper frames codon usage chiefly in terms of translation. Its direct result also concerns one antibody fragment, not antibody fragments generally. (LLM, conf=0.86)
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Sharp, P. M., & Li, W.-H. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.3.1281 · Cited by 3,992 · see citing works
Codon bias and heterologous protein expression
Gustafsson, C., Govindarajan, S., & Minshull, J. (2004) · Trends in Biotechnology · doi:10.1016/j.tibtech.2004.04.006 · Cited by 1,330 · see citing works
Multiple roles of the coding sequence 5′ end in gene expression regulation
Tuller, T., & Zur, H. (2015) · Nucleic Acids Research · doi:10.1093/nar/gku1313 · Cited by 206 · see citing works
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- Yu J, Amores J, Sebe N, Radeva P and Tian Q (2008) Distance learning for similarity estimation. IEEE Trans Pattern Anal Mach Intell 30, 451-462.
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Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments
Sandomenico, A., Sivaccumar, J. P., & Ruvo, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176324 · Cited by 134 · see citing works
“At the transcriptional level, the concept of “codon harmonization”, a sophisticated version of the codon usage optimization, has largely improved the expression of antibodies fragments [60,103].”
BackgroundCurrent structure predictors are not learning the physics of protein folding
Outeiral, C., Nissley, D. A., & Deane, C. M. (2022) · Bioinformatics · doi:10.1093/bioinformatics/btab881 · Cited by 82 · see citing works
- Authors
- Mignon, C., Mariano, N., Stadthagen, G., Lugari, A., Lagoutte, P., Donnat, S., Chenavas, S., Perot, C., Sodoyer, R., & Werle, B.
- Affiliations
- BIOASTER (FR)
- CAD4Bio Montbonnot France
- OTECI Lyon France
- Corresponding author
- Werle, Bettina
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2018-04-16
- Volume
- 592
- Issue
- 9
- Pages
- 1554-1564
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2795780418
- Cited by
- 50
- References
- 3
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 3 · 2021: 6 · 2020: 11 · 2019: 3 · 2018: 2
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- investissement d'avenir (Grant NO. ANR-10-AIRT-03, ANR-10-AIRT-03)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- codon usage, codon adaptation index, heterologous expression, translation efficiency, synonymous codons, recombinant protein yield
- MeSH terms
- Algorithms, Base Sequence, Codon, Gene Expression Regulation, Solubility, Protein Biosynthesis, Computational Biology
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