"We have demonstrated the simultaneous incorporation of two unnatural amino acids into the same polypeptide," says Professor Peter G. Schultz, Ph.D., who holds the Scripps Family Chair in Chemistry at Scripps Research. "Now that we know the genetic code is amenable to expansion to 22 amino acids, the next question is, how far can we take it?"
In an upcoming issue of the journal Proceedings of the National Academy of Sciences, the team describes how they engineered this modified form of E. coli to make myoglobin proteins with 22 amino acids -- incorporating the unnatural amino acids O-methyl-L-tyrosine and L-homoglutamine in addition to the naturally occurring 20.
Scientists have for years created proteins with such unnatural amino acids in the laboratory, but until Schultz and his colleagues began their work in this field several years ago, nobody had ever found a way to get organisms to add unnatural amino acids into their genetic code. Earlier studies by Schultz's group described the incorporation of a number of single unnatural amino acids with a variety of uses in chemistry and biology into E. coli and into the yeast Saccharomyces cerevisiae.
This latest result is a boon because it demonstrates that multiple unnatural amino acids can be added to the genetic code of a single modified organism. This proof-of-principle opens the door for making proteins within the context of living cells with three, four, or more additional amino acids at once.
The article, "A twenty-two amino acid bacterium with a functional quadruplet codon" is authored by J. Christopher Anderson, Ning Wu, Stephen W. Santoro, Vishva Lakshman, David S. King, and Peter G. Schultz and will be posted online during the week of May 10-1
Contact: Jason Bardi
Scripps Research Institute