Codon Optimization: The Key Strategy to Enhance Protein Expression Efficiency
In recombinant protein expression systems, codon optimization has become a key technical means to break through the bottleneck of heterologous gene expression. The biological basis of this strategy stems from the species-specific codon usage bias phenomenon - different organisms have formed unique codon usage frequencies through long-term evolution, and this frequency is significantly positively correlated with the abundance of tRNA pools in host cells. Taking the E. coli expression system as an example, the proportion of arginine codon AGA in its genome (21.3%) far exceeds the CGT codon preferred by mammalian cells (6.8%). This difference directly leads to the occurrence of up to 83% rare codon sites in unoptimized human genes in this system, causing a decrease in ribosome movement rate and accumulation of misfolded proteins.
