Enhancing the Production of Complex Proteins in Bacteria

Life Sciences : Research Tools

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Inventors

  • George Georgiou, Ph.D. , Chemical Engineering
  • Lluis Masip, B.S. , Chemical Engineering
  • Laura Segatori, B.S. , Chemical Engineering
  • Matthew DeLisa, Ph.D. , Chemical Engineering

Background/unmet need

Numerous therapeutic proteins contain disulfide bonds. However, the production of proteins containing multiple disulfide linkages in genetically engineered bacteria is very inefficient. Bacteria are often not able to produce complex eukaryotic proteins in an active form and in high amounts because the bacterial machinery that catalyzes the isomerization of disulfide bonds is inefficient. As a result, such proteins have to be produced in mammalian cells at a considerably higher expense.

Invention Description

The invention provides methods for using the Twin Arginine Translocation (TAT) pathway in bacteria to produce heterologous polypeptides that have multiple disulfide bonds. In addition to the composition of novel secretion mechanisms, methods of screening polypeptide libraries produced by secretion through the TAT pathway are also available. This system allows improved production of recombinant proteins with at least one disulfide bond and opens new opportunities for bacterial expression of complex proteins in a properly folded and functional form.

Benefits/Advantages

  • Increase in the production of useful and obtainable therapeutic proteins
  • Broadens the array of proteins produced by bacterial systems

Features

  • Allows production of recombinant proteins with multiple disulfide bonds
  • Can express libraries of recombinant proteins for screening or testing
  • Exploits TAT pathway

IP Status

  • 1 foreign patent application filed
  • 9 foreign patents issued

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