Scientists use artificial DNA to create semi-synthetic life
The blueprint of organisms, better known as DNA, is made up of four bases, namely adenine, guanine, cytosine and thymine (A, G, C and T). These chemical bases which store genetic information make up codons of three bases, where strings of the codons are interpreted by cellular machinery. This information results in the formation of chains of amino acids which later turn into proteins and carry out various specialized functions. The goal of synthetic biology is to create artificial bases and advance the nucleic acid systems in living organisms.
Recently, Floyd Romesberg of the Scripps Research Institute in La Jolla, California, and his colleagues have revealed an engineered organism they developed which incorporates both natural and artificial DNA using novel X and Y bases, which is capable of creating entirely new, synthetic proteins. They published their study in the journal, Nature.
In the study, the organism was instructed to make a modified version of Green Fluorescent Protein (GFP), which is extensively used in research. This was chosen for convenience, since it was easy to measure the amount of protein produced, Romesberg said. In one experiment, they demonstrated that an artificial codon could be used to insert a single molecule of a natural amino acid into GFP. In the second experiment they tried inserting one artificial amino acid, followed by a second one, into the GFP. The artificial amino acids they used resembled natural ones, however they carried an additional chemical group, which allowed the researchers to identify them. In both the cases, they observed that more than 95% of the protein produced by the bacteria contained the synthetic buildingS block in question.
“This is the first time ever a cell has translated a protein using something other than G, C, A or T,” Romesberg said. “The improved bacterium uses its synthetic DNA to make amino acids with the same efficiency as natural DNA”. This is a goal Romesberg has been working towards for the past 20 years. However, creating new forms of life is not the main point. Romesberg is interested in using this expanded genetic alphabet to create new types of proteins which can be used to treat disease.
Expanding the DNA alphabet from four letters to six allows it to code for many more amino acids. The hope is that one day this method could be used to make new drugs, polymers or catalysts. Proteins made using synthetic ingredients could be more easily altered to have desirable therapeutic properties such as lasting longer or more powerful when compared to the natural sort.
Romesberg is aware that the creation of semi-synthetic organisms might raise concerns of hybrid life forms spreading beyond the lab, however the system they used makes such an escape unlikely. This is because the artificial bases cannot bond with natural bases. And furthermore, because cells cannot make their own X and Y without the addition of certain chemicals, these semi-synthetic organisms cannot live outside of a laboratory.
Romesberg next hopes to extend the bacterium’s genetic vocabulary. Synthorx, a Scripps Research spinoff, was formed in San Diego to commercialize the discovery. It is now preparing to begin development of drugs, starting with cancer or autoimmune diseases.
Zhang, Y. et al. (2017). A semi-synthetic organism that stores and retrieves increased genetic information. Nature 551, 644–647.