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A team of biochemists from the University of Pennsylvania (Penn) School of Medicine have built a completely new type of protein from scratch using design and engineering principles learned from nature. Their findings appear in the most recent issue of Nature. According to the university Web site, current protein engineers use existing biochemical scaffolds from nature and alter them to make them do something else.
“This research demonstrates how we used a set of simple design principles, which challenge the kind of approaches that have been used to date in reproducing natural protein functions,” said senior author P. Leslie Dutton, PhD, Eldridge Reeves Johnson, professor of biochemistry and biophysics, in a report by the university. The natural design of proteins ultimately lies in their underlying sequence of amino acids. This sequence of amino acids for a particular protein is determined by the sequence of nucleotides in messenger RNA. and it is the order of the amino acids and the chemical bonds between them that establish how a protein folds into its final shape.
According to the report, this protein was engineered to transport oxygen to some day be used to make artificial blood for use by emergency-care professionals. To build the protein, the researchers began with three amino acids, which code for a helix-shaped column, and from this, they assembled a four-column bundle with a loop and added a heme—a chemical group that contains an iron atom to bind oxygen molecules. They also added glutamate to help the columns open up to capture the oxygen. Since heme and oxygen degrade in water, the researchers also designed the exteriors of the columns to repel water to protect the oxygen payload inside.
“Our aim is to design new proteins from principles we discover studying natural proteins,” explained co-author Christopher C. Moser, PhD, associate director of the Johnson Foundation at Penn, in the university report. “For example, we found that natural proteins are complex and fragile and when we make new proteins we want them to be simple and robust. That’s why we’re not re-engineering a natural protein but making one from scratch.”
According to the report, the team initially used robotics to determine the sequence of amino acids, then they used E. coli as a biological host to make the full protein. Tests confirmed that their protein did capture oxygen. "Our approach to building a simple protein from scratch allows us to add on, without getting more and more complicated,” said Dutton, in the report.