All life we know shares one common feature: DNA. From bacteria to humans, our genetic code is written in the same 4 chemical “letters”, the nucleotides Adenine (A), Thymine (T), Guanine (G) and Cytosine (C) – at least until recently. Last month, researchers from The Scripps Research Institute in California reported that they have successfully inserted 2 artificial nucleotides into DNA and generated an organism which could retain their semi-synthetic DNA in a stable manner ¹.

These new letters could greatly extend the genetic code, which produces 20 “words” in its original form. The cell can translate these words into 20 amino acids – the building blocks of all cellular proteins. Dr Floyd Romesberg, the leading scientist of the study, explains that having 2 additional letters “allows for the encoding of proteins containing more unnatural amino acids than we could ever possibly use”. This could enable us to create completely novel, non-naturally occurring proteins, which could be used as drugs or nanomaterials.

The breakthrough of the current study is that DNA containing the 2 new nucleotides designed by Dr Romesberg’s team could not only be replicated in the lab, but also by a living organism. The researchers introduced their semi-synthetic DNA into the bacterium E. coli, and what they observed was surprising: “Once we had them [the new nucleotides] inside the cell the absolutely normal replication machinery of E. coli […] recognized our unnatural nucleotides perfectly fine and replicated them with high efficiency and fidelity. We actually didn’t have to do any manipulation of the cell to get them to take the unnatural [letters] once we had it in the cell.” ²

His laboratory is already working on the next step to make the organism produce synthetic proteins, which is helping the bacterium read and translate the new information encoded in its DNA. Once the cell can do this, producing novel proteins will be much faster and cheaper than it is by chemical means – and this could pave the way for the widespread use of human-designed proteins.

Edited by Debbie Nicol

1. Malyshev, D. A. et al. A semi-synthetic organism with an expanded genetic alphabet. Nature. (2014)
2.  Link to article here.