Princeton Innovation: Hecht and Zarzhitsky: Insulin production using artificial proteins

A novel method for producing insulin at lower cost and with greater efficiency could help provide this life-sustaining medication to the estimated 450 million diabetes sufferers around the world. This new method of making the drug uses artificial, or de novo, proteins created from synthetic genes designed by researchers in the lab of Michael Hecht, a professor of chemistry.

Insulin is a protein consisting of two peptide chains connected by three bridges in the form of molecular bonds. The drug is currently made by programming the genetic sequence for human insulin into bacteria, which produce human insulin as a long, three-part peptide chain that requires folding to bring the two peptide chains together, followed by the removal of the middle section that links the two chains.

With the new method, researchers replace the middle section with a synthetic sequence encoding an artificial protein. Compared to the current method, the artificial protein brings the two insulin chains together more effectively. Moreover the de novo protein is easier to express, is highly stable, and is easily purified without an additional tag. Unlike the current method, which brings the two chains together correctly about 70 percent of the time, this new method using the artificial protein is nearly 100 percent efficient at making insulin.

Shlomo Zarzhitsky, a postdoctoral researcher working with Hecht, recognized the value of using these artificial proteins, called de novo expression enhancer proteins, or DEEPs, for joining together peptides to make insulin. The technology can also be used to make other proteins and peptides that are difficult to express.

“These are proteins that do not occur in nature,” Zarzhitsky said. “They have advantages in that they are very stable and small, so they do not impose a burden on the bacterial protein expression machinery.”

The technology represents the application of synthetic biology to the search for therapeutic proteins, Hecht said.

This story first appeared at Celebrate Princeton Innovation on November 8, 2018. The video was added on May 3, 2019. See the original story here.