DNA Code Gets Two New Synthetic Letters—And Uses Them to Create a New Protein

Researchers hope the advance is a step toward producing a range of new compounds, including designer drugs and biofuels

Glowing DNA
Glowing proteins produced by the modified E. coli. Bill Kiosses/The Scripps Research Institute

As many may know from the movie GATTACA, all DNA is composed of nucleotides containing one of four bases: A, C, G and T. These letters are the “blueprint” for life that has evolved over billions of years, pairing off to create DNA's distinctive double helix structure. But as Sarah Kaplan reports for The Washington Post, researchers have added two new letters to DNA’s short alphabet, creating bacteria that can synthesize amino acids not normally produced by living organisms. 

According to the Associated Press, in 2014 researchers as The Scripps Research Institute in La Jolla, California, were able to add two new bases, called X and Y, to the DNA of a laboratory strain of E. coli bacteria. As Kaplan reports, those bacteria were unstable, losing their Xs and Ys after a few days.

Earlier this year, the team was finally able to create a stable form of that modified bacteria—but the updated version still couldn't use its synthetic bases, reports Ewen Callaway at Nature. In the latest experiment, however, the E. coli were actually able to use their expanded alphabet to create unnatural amino acids, which combined with others to produce glowing green proteins. The research appears in the journal Nature.

According to the AP, it’s still early days, but the goal of this type of artificial DNA programming is to create organisms capable of producing compounds that can have a wide range of purposes, including designer drugs or biofuels. Perhaps researchers could even create organisms capable attacking cancer cells or suck up oil spills.

As Callaway reports, the four naturally occurring DNA bases can combine in 64 different three-letter pairings, also known as codons, the recipe for an amino acid. But because several different codons create the same amino acid, only 20 amino acids form the basis for almost all proteins in nature. Adding the X-Y base pair to the system could add another 100 amino acids possibilities to the mix.

“It’s wave front stuff; this is the edge of science,” University of Texas at Austin biochemist Andrew Ellington, not involved in the research, tells Kaplan. “We are better learning how to engineer living systems.”

The Scripps team is not the only group working on synthetic DNA. Callaway reports that scientists have modified DNA bases since 1989 and that researchers at the Institute of Bioengineering and Nanotechnology in Singapore have created a similar system in test tubes, not in living cells.

Not everyone is convinced the team has made a breakthrough. Steve Benner, biochemist at the Foundation for Applied Molecular Evolution, tells Kaplan that he thinks the natural E. coli DNA is producing the amino acids despite having the alien DNA in the mix. But Floyd Romesberg, head of the research laboratory at Scripps where the work is being done, counters that the glowing green protein is proof that the E. coli is using the X and Y bases to produce an unnatural amino acid. Callaway points out that other critics think the way that the X and Y bases stick togther—a method similar to the way grease clumps together—is not stable enough for this type of system to grow more complex.

Even if this particular method doesn't lead to the designer drug revolution, the experiment raises the possibility that there could be alternate forms of life based on a similar but different DNA-like system. “It suggests that if life did evolve elsewhere, it might have done so using very different molecules or different forces,” Romesberg tells Antonio Regalado at MIT Technology Review. “Life as we know it is may not be the only solution, and may not be the best one.”

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