Columbia Technology Ventures

Targeted Mutagenesis and Codon Selection Techniques to Improve Protein Expression and Solubility

Protein expression and solubility is necessary for the production of enzymes for research, industrial drug and food production, and many other processes. The demand for large-scale production of soluble protein necessitates high yields with high solubility. However, some proteins are more difficult to express than others, and generating high yields may be hindered by low solubility. Therefore, new methods for improving protein expression and solubility without affecting protein function are in high demand. This technology utilizes an algorithm called Columbia Metric to identify proteins with limited expression and solubility due to poor codon usage and provides a method for increasing protein expression and solubility via codon optimization.

Codon selection technology increases protein yield and efficiency by improving protein expression and solubility

Large-scale data mining studies of protein expression revealed that several amino acids and codons correlated with higher expression and solubility of proteins expressed in E. coli. Within the amino acids that improved protein expression and solubility, specific codons for these amino acids were correlated with higher expression and solubility, whereas other codons for the same amino acid were unfavorable for expression and solubility. This technology aims to enhance protein production by improving codon usage. This method was tested on a variety of target proteins resulting in significant improvements in the expression and solubility of the engineered proteins. An advantage of this technology is that it improves codon usage without affecting the protein sequence or function. Thus, this technology provides industrial and pharmaceutical companies a potential method for increasing the efficiency of protein expression, which may ultimately lower production costs.

Lead Inventor:

John F. Hunt, Ph.D.

Applications:

  • A metric to identify proteins whose expression is limited by poor codon usage
  • A method for altering the yield of soluble recombinant polypeptides.
  • A method to predict the solubility, expression, and usability of polypeptides.
  • To enhance protein expression and solubility without altering protein function for industrial and commercial applications such as food production, drug discovery, and drug production.

Advantages:

  • Other codon optimization methods rely on using the more common codons for optimization, but this technology takes into account more specific solubility and expression knowledge of specific amino acids and codons.
  • Codon usage is improved without affecting the protein sequence or function

Patent information:

Patent Pending (PCT/US2011/024251)

Tech Ventures Reference: IR M10-014

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