Adjustment of codon usage frequencies by codon harmonization improves protein expression and folding

Area of Science:

• Biotechnology
• Molecular Biology
• Protein Expression

Background:

• Prokaryotic expression systems are crucial for bioproduction of therapeutic proteins.
• Heterologous protein expression relies on optimizing translation and folding, but remains empirical.
• Current methods include codon usage, tRNA, and chaperone co-expression.

Purpose of the Study:

• To improve heterologous protein expression and yield.
• To develop a computational approach for optimizing protein production.
• To enhance the production of soluble and functional therapeutic proteins.

Main Methods:

• Developed a novel algorithm named "codon harmonization."
• The algorithm adjusts codon usage frequencies for heterologous systems based on native host data.
• Applied the method to optimize protein expression in Escherichia coli.

Main Results:

• The codon harmonization algorithm successfully improved heterologous protein expression.
• The method may enhance protein folding during translation.
• Demonstrated potential for improving soluble, functional protein production.

Conclusions:

• Codon harmonization offers a promising strategy for enhancing heterologous protein expression.
• This approach could be broadly applicable across different prokaryotic hosts.
• Further research may refine this method for general use in biopharmaceutical production.