Synthetic DNA used to make proteins in living cells

It is the first time that bacteria have been able to produce proteins coded in genes written in an augmented DNA 'alphabet'. Scientists at the Scripps Research Institute in California had previously described being able to modify bacterial cells to use the extra synthetic letters, or 'bases', in their DNA. This gave them an X and a Y, along with the A, C, G and T that all other organisms use (see BioNews 886). Now, genes using X and Y have been shown to work, producing a functional protein, according to a paper published in the journal Nature. 

'There is no biological system so fundamental and more intimately related to what we are than information storage and retrieval,' study lead author Professor Floyd Romesberg, told Nature News. 'What we've done is design a new part that functions right alongside the existing parts and can do everything they do.'

The researchers gave Escherichia coli the molecular tools required to make sense of the new bases, allowing it to read DNA containing X and Y. This it could transcribe into RNA, which is used as a template for translating into protein. Organisms use combinations of three letters, called codons, to specify which amino acids go where in a protein. In this study, the researchers inserted the synthetic bases into a codon in a gene which produces a fluorescent protein.

Not only were the bacteria using codons containing the new bases, but, building on the work of previous groups, the researchers made the bacteria use those codons to make the cells incorporate synthetic amino acids that do not appear in nature. These 'non-canonical' amino acids represent a thriving area of synthetic biology research, as they potentially allow scientists to add novel chemical properties to proteins.

This expansion of the genetic alphabet is another milestone achievement for the field of synthetic biology. This field could eventually give living organisms new and useful properties not found in nature. However, the bacteria in this study have a long way to go to fulfill these aspirations.

These 'semi-synthetic organisms' have only currently been shown to use X and Y in one codon at a time. They were not dispersed throughout the genome like the four natural bases are. They were also only used in a protein known to be very tolerant of alteration. This paper also only describes two novel codons using X and Y, although Professor Romesberg said that the group has identified 12 more that work. 

'This was the smallest possible change we could make to the way life works – but it is the first ever,' said Professor Romesberg.