Chemist Floyd Romesberg of the Scripps Research Institute in La Jolla, California, and his colleagues manipulated Escherichia coli bacterial cells to incorporate two types of foreign chemical bases, or letters, into their DNA. The cells then used that information to insert unnatural amino acids into a fluorescent protein.
These form pairs that hold together DNA’s double helix, and different three-letter sequences code for each of the 20 amino acids that make up the proteins in living cells.
The new work is the first to show that unnatural bases can be used to make proteins within a living cell. These “Funny” DNA letters, as Benner has called them, could replicate and make RNA and proteins in test-tube reactions.
To function in living cells the foreign base pairs need to sit alongside natural bases without disturbing the shape of DNA or disrupting essential tasks, such as the processes that faithfully copy DNA and transcribe it into messenger RNA-an intermediary molecule between DNA and proteins.
The ‘alien DNA’ was made of chemicals called dNaM and d5SICS. But the cells divided sluggishly, and tended to lose their foreign DNA over time.
In the latest research, reported in Nature on November 29, the team created healthy cells that can finally wield their foreign DNA. In separate experiments, the cells incorporated two unnatural amino acids into a protein that emits a soft, green glow.