ArticleBMC biology2021
Assessing optimal: inequalities in codon optimization algorithms.
Article in BMC biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 43 citations in OpenAlex.
- Double-stranded DNA donors and CRISPR-Cas9 for universal correction of mutations causing cystic fibrosis in human airway cells.Molecular therapy. Nucleic acids · 2026Article
- Enhancing protein expression in humans through codon optimization with transformer and contrastive learning.Molecular therapy. Nucleic acids · 2026Article
- pCODE tRNA Expression Plasmids Compensate for Rare Codons in Recombinant Protein Production.ACS synthetic biology · 2026Article
- Cross-species gene redesign leveraging ortholog information and generative modeling.Nature communications · 2026Article
- DeepCodon: A deep learning codon-optimization model to enhance protein expression.Biodesign research · 2025Article
- Near-cognate tRNAs dominate codon decoding times in simulated ribosomes.Nucleic acids research · 2025Article
- Integrating Structural Bioinformatics and Functional Mechanisms of Sesquiterpene Synthases CARS and CADS inInternational journal of molecular sciences · 2025Article
- The Achilles Heel of Protein Biochemistry: Insolubility of Recombinant Proteins-A Case Study About Producing a Rice Enzyme.International journal of molecular sciences · 2025Article
- Article
- Mechanistic Insights into the Bornyl Diphosphate Synthase fromCurrent issues in molecular biology · 2025Article
- Modeling coding sequence design for virus-based expression in tobacco.Synthetic and systems biotechnology · 2025Article
- Comparative Analysis of Codon Optimization Tools: Advancing toward a Multi-Criteria Framework for Synthetic Gene Design.Journal of microbiology and biotechnology · 2025Article
- CodonTransformer: a multispecies codon optimizer using context-aware neural networks.Nature communications · 2025Article
- The Production of Complement Inhibitor Proteins in Mammalian Cell Lines-Light at the End of the Tunnel?Biomedicines · 2024Review
- An exploratory in silico comparison of open-source codon harmonization tools.Microbial cell factories · 2023Article
- Genes for highly abundant proteins in Escherichia coli avoid 5' codons that promote ribosomal initiation.PLoS computational biology · 2023Article
- Using protein-per-mRNA differences among human tissues in codon optimization.Genome biology · 2023Article
- Computational formulation of a multiepitope vaccine unveils an exceptional prophylactic candidate against Merkel cell polyomavirus.Frontiers in immunology · 2023Article
- Engineering ofMetabolic engineering communications · 2022Article
- Codon-specific Ramachandran plots show amino acid backbone conformation depends on identity of the translated codon.Nature communications · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCustom genes have become a common resource in recombinant biology over the last 20 years due to the plummeting cost of DNA synthesis. These genes are often "optimized" to non-native sequences for overexpression in a non-native host by substituting synonymous codons within the coding DNA sequence (CDS). A handful of studies have compared native and optimized CDSs, reporting different levels of soluble product due to the accumulation of misfolded aggregates, variable activity of enzymes, and (at least one report of) a change in substrate specificity. No study, to the best of our knowledge, has performed a practical comparison of CDSs generated from different codon optimization algorithms or reported the corresponding protein yields.
resultsIn our efforts to understand what factors constitute an optimized CDS, we identified that there is little consensus among codon-optimization algorithms, a roughly equivalent chance that an algorithm-optimized CDS will increase or diminish recombinant yields as compared to the native DNA, a near ubiquitous use of a codon database that was last updated in 2007, and a high variability of output CDSs by some algorithms. We present a case study, using KRas4B, to demonstrate that a median codon frequency may be a better predictor of soluble yields than the more commonly utilized CAI metric.
conclusionsWe present a method for visualizing, analyzing, and comparing algorithm-optimized DNA sequences for recombinant protein expression. We encourage researchers to consider if DNA optimization is right for their experiments, and work towards improving the reproducibility of published recombinant work by publishing non-native CDSs.
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