How do you stop genetically engineered organisms from surviving and procreating outside the lab? Fictional scientists in Jurassic Park thought they had cracked it. But boy, were they wrong.
Now GM bacteria have been designed that can survive for hundreds of generations as long as they are fed nutrients that don’t occur naturally. This, the researchers hope, will allow us to make use of GMOs while ensuring they can never survive on their own in the wild.
Synthetic biologists design organisms to carry out useful functions, like synthesising drugs or breaking down waste products. But making sure engineered genes stay where you put them has been a challenge.
“We need to have biosafety features that allow you to ensure that when you’ve made something it’s not going to escape from the lab, or if it does it won’t be able to prosper,” says Andrew Ellington at the University of Texas at Austin.
There are 20 naturally occurring amino acids, which our bodies assemble to create proteins.
In Jurassic Park, fictional scientists made the dinosaurs unable to produce lysine, one of the natural amino acids, so they would need lysine supplements. In reality, all animals are unable to synthesise lysine, but, as the dinosaurs showed in the film, it is easy to find it in our diet.
Unnatural amino acids
Ellington’s solution should be more effective. His team has engineered E. coli bacteria to make proteins using an unnatural amino acid.
To do so, the researchers reengineered the gene TEM-1 β-lactamase, which confers resistance to an antibiotic, altering it so that an unnatural analogue of an amino acid was used in the creation of its protein. They also induced mutations in part of the gene coding for six nearby amino acids so that the artificial amino acid made contact with them, and then selected for mutations that restored the function of the protein.
This led to the bacteria having a modified, yet functioning, gene that gave them antibiotic resistance.
But the bacteria could not return to using the natural amino acid, since it would no longer fit in that part of the protein.
As a result, the bacteria will die if they don’t have the unnatural amino acid. They were grown in the lab for hundreds of generations without evolving out of their reliance on it.
“In the presence of antibiotics and the absence of the [artificial] amino acid, there’s very little way for our circuitry to leave the lab,” says Ellington.
Two studies last year achieved the same feat by modifying the whole genome of E. coli. But Ellington’s method would be much easier to apply to other organisms, since dependence on the unnatural amino acid is established by a single gene that can be easily transferred between organisms.
Apart from helping to contain bacteria engineered to do useful things for us, such as making fuel or fighting tooth decay, getting them to use unnatural amino acids could give synthetic biologists a bigger toolkit to work with.
But persuading bacteria to evolve new functions has proven a challenge. “No one’s been able to evolve proteins that use unnatural amino acids in interesting ways,” says Floyd Romesburg at the Scripps Research Institute in La Jolla. “Basically what we’ve been able to do is simply coax organisms into having the unnatural amino acid there, but it’s pretty fragile and you could lose it easily.”
Ellington’s method addresses that problem by reengineering the protein to create a pressure to maintain the unnatural amino acid.
This may be valuable for designing drugs that improve on naturally occurring proteins, says Ellington: “Proteins used as drugs will need tweaking. The ability to tweak them and use functionality that’s not provided by the natural amino acids is significant.”
Journal reference: Nature Chemical Biology, DOI: 10.1038/nchembio.2002
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