Synthetic biology: The proof is in the protein

A semi-synthetic organism that can both store and retrieve unnatural, man-made genetic information is described in this week’s Nature. The bacterium could serve as a platform for the creation of new proteins and functionalities.

The genetic code is made of four nucleotides, adenine, cytosine, guanine and thymine, which pair to form the rungs of the DNA double helix. In 2014, Floyd Romesberg and colleagues described a semi-synthetic strain of the bacterium Escherichia coli that incorporated an extended genetic code containing two unnatural nucleotides in addition to the four natural nucleotides that pair to form the DNA double helix. The bacterium could maintain and reproduce the altered genetic code, but it was unclear whether the unnatural nucleotides could be used to encode protein like normal DNA.

Romesberg and co-authors now show that the bacterium transcribes and translates the unnatural nucleotides, with the same efficiency as the natural nucleotides, to synthesize protein containing unnatural amino acids. The semi-synthetic organism is able to make protein that contains unnatural amino acids with no loss in efficiency in comparison to natural proteins.

Creating organisms that are designed to make modified, non-natural proteins has been a long-standing goal of synthetic biology. The research paves the way for scientists to engineer new proteins with unnatural amino acids, and provides a route to making novel therapeutics, plastics and other materials.