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Codon Optimization

Codon optimization is a gene design engineering technique that improves levels of protein production without altering amino acid sequences. In molecular biology, each protein sequence comprises only 20 standard amino acids; however only a few amino acids are encoded by a single codon. Most amino acids are encoded by two to six different codons, and those codons for the same amino acid are known as synonymous codons. Interestingly, the use of synonymous codons is not random in numerous organisms, and the phenomena is known as codon bias, which is the key to codon optimization.  

Codon bias, a characteristic pattern of preference in the usage of synonymous codons in highly and lowly expressed genes, has been shown to be correlated to expression levels of a gene and is a dominant method in designing synthetic genes for translational efficiency. For highly express genes in E. coli and yeast, codon bias is found to be related with tRNA abundance. Since its importance to codon optimization, it has been quantified by various calculations, including the frequency of relative synonymous codon usage, codon bias index, use of optimal codons, effective number of codons, and codon adaptation index. In another aspect, widely adopted technology of synthetic DNA for codon optimization is called codon randomization. This method utilizes tables of translation according to frequency distribution of codons in an entire genome or a subset of genes of highly expressed codons.

Creative Enzymes offers the codon optimization service for various organisms based on considerations of many factors related to different stages of protein expression. With years of experience in codon optimization and DNA synthesis for almost all major expression systems, we offer professional one-stop services:

References:

  1. Al-Hawash, A.B., Zhang, X., Ma, F. (2017) Strategies of codon optimization for high-level heterologous protein expression in microbial expression systems. Gene Reports. 9: 46-53.
  2. Papamichail, D., Liu, H., Machado, V., Gould, N., Robert Coleman, J., Papamichail, G (2018) Codon Context Optimization in Synthetic Gene Design. IEEE/ACM Transactions on Computational Biology and Bioinformatics. 15: 452-459.

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Enzyme Expression and Production

A possible reason for the observed codon bias is that amino acids similar in both size and hydrophobicity tend to share similar codon pattern, which minimizes the impact of random mutagenesis. Figure 1. A scheme showing codon bias. Most often used nucleic acids are color-coded. A possible reason for the observed codon bias is that amino acids similar in both size and hydrophobicity tend to share similar codon pattern, which minimizes the impact of random mutagenesis.



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