Hannah Kazis-Taylor

A team of researchers from Yale and Northwestern published a paper detailing a new method of incorporating synthetic amino acids into proteins. This new technology has far-reaching applications across many fields, including pharmaceutical-drug design, surgical adhesives and environmental sensors, according to the researchers involved.

The paper describes a newly developed method that improves upon previous biotechnology research. The new method  manipulates cellular machinery so that it can incorporate “multiple instances of a single synthetic amino acid” per protein chain, according to study co-author Miriam Amiram, a postdoctoral scholar in the Yale Isaacs Lab, which develops “foundational genomic and cellular engineering technologies.”

According to the paper, the new method recodes the DNA of E. coli bacteria, making it possible for the responsible enzyme to attach tRNA to synthetic amino acids. Unlike the 22 amino acids found in naturally occurring proteins, synthetic amino acids are manmade. The new technique incorporates the synthetic amino acids into polypeptides, and is the culmination of three and a half years of work by the Isaacs, Söll and Rinehart Labs at Yale as well as research conducted at Northwestern.

“This paper really describes a highly evolved tool, if you will, or a more advanced technology that is very distinct in its performance and its capabilities, and it’s distinct from anything that we’ve ever worked on before,” said Jesse Rinehart GRD ’04, study co-author and professor of cellular and molecular physiology.

Previous research, which was partly conducted at Yale, succeeded in modifying the DNA of E. coli bacteria so that the cell incorporated a few synthetic amino acids in a protein. The previous procedure necessitated modifying a “stop” codon — the code that indicates to cellular machinery that a protein should end — to code for a synthetic amino acid that researchers introduce to the cell. But the mechanism responsible for translating this modified DNA into protein chains was inefficient, Amiram said. Rinehart said this previous approach limited both the number of synthetic amino acids that can be incorporated, and the overall purity of the finished proteins. The team solved the overarching problem of the cell’s inefficient translation machinery by manipulating the cell so that the enzyme responsible for attaching synthetic amino acids to tRNA operates more efficiently, resulting in “up to 25-fold increased protein production.”

According to study co-author Adrian Haimovich GRD ’18 MED ’18, graduate student in the Isaacs Lab, the ultimate outcome of the paper was twofold. The team both created, to facilitate their own research, new enzymes, and developed a new technique that others can use to engineer improved enzymes for their own work, Haimovich said.

The study was published in Nature Biotechnology on Nov. 15.