What is PyIRS? And why is it so versatile?

A Chemical & Engineering News (C&EN) article by Celia Henry Arnaud explains that our cells rely on 20 established amino acids to engineer proteins. Our body employs biological machinery to identify each amino acid and attach it to its corresponding transfer RNA molecule. With these tools, the cell's ribosome can synthesize proteins. 

But, one transfer RNA molecule, the pyrrolysyl-tRNA synthetase (PyIRS) can, unlike its peers, "be adapted to accept many different nonnatural amino acids but doesn't recognize the canonical ones," according to Celia. That means the flexible PyIRS offers a critical test point for nonnatural amino acid discovery and development.

Now, CCB Professor David R. Liu's group and Yale University's Dieter Söll Lab have investigated exactly what makes PyRIS choose nonnatural amino acids and reject the canonical. Their collaboration resulted in two publications from Nature Chemical Biology. Wenshe Liu, who studies protein evolution at Texas A&M University, said: "The work presented here allows for aminoacyl-tRNA synthetase (aaRS) evolution over multiple generations on a practical timescale," and "suggest that this new method for aaRS evolution can yield aaRS mutants with considerable improvements in activity and specificity."