ArticleMicrobial cell factories2021
Codon pair optimization (CPO): a software tool for synthetic gene design based on codon pair bias to improve the expression of recombinant proteins in Pichia pastoris.
Article in Microbial cell factories, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 30 citations in OpenAlex.
- Beyond codon optimality: codon pairs regulate mRNA stability dependent on translation.bioRxiv : the preprint server for biology · 2026Article
- Metabolic engineering ofApplied and environmental microbiology · 2026Review
- Evolution and Functional Implications of Codon Usage Bias in Eukaryotes.Journal of molecular evolution · 2026Review
- Scalable secretory production of influenza A (H1N1) hemagglutinin HA1 in Pichia pastoris through expression and process optimization.Microbial cell factories · 2026Article
- Multidimensional Gene Space as an Approach for Analyzing the Organization of Genomes.International journal of molecular sciences · 2025Article
- Uncovering position-specific patterns in codon and codon-pair usage in candidate genes associated with blood coagulation diseases.NAR genomics and bioinformatics · 2025Article
- Therapeutic implications of synonymous gene recoding: insights into mechanisms controlling protein biogenesis and activity.Protein & cell · 2025Article
- Unravelling Prokaryotic Codon Usage: Insights from Phylogeny, Influencing Factors and Pathogenicity.Current genomics · 2025Review
- Link Between Individual Codon Frequencies and Protein Expression: Going Beyond Codon Adaptation Index.International journal of molecular sciences · 2024Article
- Synthetic biology approach revealed enhancement in haeme oxygenase-1 gene expression by codon pair optimization while reduction by codon deoptimization.Annals of medicine and surgery (2012) · 2024Article
- Traditional uses, phytochemistry, pharmacology, toxicity and clinical application of traditional Chinese medicineFrontiers in pharmacology · 2024Review
- Dicodon-based measures for modeling gene expression.Bioinformatics (Oxford, England) · 2023Article
- Synonymous Codon Variant Analysis for Autophagic Genes Dysregulated in Neurodegeneration.Molecular neurobiology · 2023Article
- Insights into Synonymous Codon Usage Bias in Hepatitis C Virus and Its Adaptation to Hosts.Pathogens (Basel, Switzerland) · 2023Article
- Application of codon usage and context analysis in genes up- or down-regulated in neurodegeneration and cancer to combat comorbidities.Frontiers in molecular neuroscience · 2023Article
- gtAI: an improved species-specific tRNA adaptation index using the genetic algorithm.Frontiers in molecular biosciences · 2023Article
- The α-mating factor secretion signals and endogenous signal peptides for recombinant protein secretion in Komagataella phaffii.Biotechnology for biofuels and bioproducts · 2022Article
- Advances in Cell Engineering of theMetabolites · 2022Review
- Evolution and host adaptability of plant RNA viruses: Research insights on compositional biases.Computational and structural biotechnology journal · 2022Review
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7 authors at 1 institution in 1 country.
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Abstract
backgroundCodon optimization is a common method to improve protein expression levels in Pichia pastoris and the current strategy is to replace rare codons with preferred codons to match the codon usage bias. However, codon-pair contexts have a profound effect on translation efficiency by influencing both translational elongation rates and accuracy. Until now, it remains untested whether optimized genes based on codon pair bias results in higher protein expression levels compared to codon usage bias.
resultsIn this study, an algorithm based on dynamic programming was introduced to develop codon pair optimization (CPO) which is a software tool to provide simple and efficient codon pair optimization for synthetic gene design in Pichia pastoris. Two reporters (MT1-MMP E2C6 and ADAM17 A9B8 scFvs) were employed to test the effects of codon pair bias and CPO optimization on their protein expression levels. Four variants of MT1-MMP E2C6 and ADAM17 A9B8 for each were generated, one variant with the best codon-pair context, one with the worst codon-pair context, one with unbiased codon-pair context, and another optimized based on codon usage. The expression levels of variants with the worst codon-pair context were almost undetectable by Western blot and the variants with the best codon-pair context were expressed well. The expression levels on MT1-MMP E2C6 and ADAM17 A9B8 were more than five times and seven times higher in the optimized sequences based on codon-pair context compared to that based on codon usage, respectively. The results indicated that the codon-pair context-based codon optimization is more effective in enhancing expression of protein in Pichia pastoris.
conclusionsCodon-pair context plays an important role on the protein expression in Pichia pastoris. The codon pair optimization (CPO) software developed in this study efficiently improved the protein expression levels of exogenous genes in Pichia pastoris, suggesting gene design based on codon pair bias is an alternative strategy for high expression of recombinant proteins in Pichia pastoris.
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