Researchers Create Unnatural Proteins by Expanding the Amino Acid Dictionary

The 20 natural amino acids, each with their own chemical properties, can be strung together in any way to make a protein. As a result, proteins have an incredibly diverse set of functions: everything from catalyzing chemical reactions to bolstering the structure of cells. While scientists have become more capable of designing and engineering proteins, the restriction of only using the 20 natural amino acids still hinders more creative scientific endeavors. A new study has transcended this limit by creating a system for including unnatural amino acids into proteins. 

In this study, a group of researchers from Scripps University designed a process where unnatural amino acids corresponded to four RNA bases instead of the usual three. When translating from RNA, each amino acid is encoded by a trio of RNA bases called a codon. For example, AGG encodes the amino acid Arginine. Nearly all possible codons have a corresponding amino acid. Prior efforts to include unnatural amino acids have tried to redesign the codon-amino acid relationship, but that requires reworking a great deal of cellular machinery. In their system, these researchers instead created custom transfer RNAs – the molecules which match up codons and amino acids – that match to four RNA bases. Since they’re just adding on to existing cellular machinery, all parts of their system can be introduced into a cell without having to change or disable natural processes. After a lot of work optimizing their system and their transfer RNAs, they manufactured diverse sets of proteins with multiple kinds of unnatural amino acids.

Different unnatural amino acids have different chemical properties and including them in a protein will have an array of uses: fine-tuning a protein’s function, labeling proteins for research, even making protein-based drugs last longer after being taken. Designing and producing custom proteins is a difficult enough process, and adding in amino acids that aren’t native to the cell adds layers of complexity on top. Their quadruplet codon system will do a great deal to simplify that complexity and open up future possibilities for new kinds of proteins.

This study was conducted by Alan Costello as part of his postdoctoral research in the lab of Ahmed Badran, an Assistant Professor of Chemistry at Scripps University

Corresponding Author: Alex Yenkin

Press Article: “Genetic Alphabet Expanded to Create New Proteins” GenEngNews

Original Article: “Efficient genetic code expansion without host genome modifications“, Nature Biotechnology
Image Credit: Flickr, Courtesy of Pacific Northwest National Laboratory