Out of thousands of possible kinds of amino acid, virtually all organisms use just 20 to build the proteins they need. Now, scientists have expanded this palette by coaxing some cells from mice to make proteins that include synthetic amino acids.
The researchers have already used the customized proteins to study basic cell biology, but the technique could someday make novel proteins for medicine or biotechnology, says study coleader Lei Wang of the Salk Institute for Biological Studies in La Jolla, Calif. “With a much larger set of amino acids, you can introduce novel biological properties into cells,” Wang says.
To use an amino acid, a cell must first attach it to a molecule of a type called transfer RNA (tRNA). One end of a tRNA grips the amino acid while the other end matches up with a specific sequence in the cell’s genetic code. The researchers needed a tRNA that could hold the artificial amino acid as well as enzymes that would make the two molecules link up.
To prevent interference with the cell’s own tRNAs, Wang’s team used Escherichia coli‘s bacterial tRNA, which operates somewhat differently than the mammalian variety does. They then tested billions of slightly different enzymes to find ones that would attach the tRNA to the three kinds of synthetic amino acids used in the study. After the researchers inserted the genes for the tRNAs and the enzymes into cultured mouse-nerve cells, the cells made proteins that incorporated the artificial amino acids. The results are in an upcoming Nature Neuroscience.