Stable bacteria created using synthetic DNA

Scientists have developed bacteria which can live and grow with DNA containing extra 'letters'.

The modified cells' DNA contains an additional two bases to the four found in nature, theoretically expanding the genetic alphabet. The scientists say the cells 'lay the foundation for achieving the central goal of synthetic biology: the creation of new life forms and functions'.

The same team from the Scripps Research Institute in La Jolla, California, had first reported the creation of such 'semi-synthetic organisms' in 2014 (see BioNews 753). However, the synthetic bases – referred to as X and Y – caused the bacteria to grow more slowly, and the cells would frequently remove the bases from their DNA over cycles of cell division.

'Your genome isn't just stable for a day,' said Professor Floyd Romesberg of the Scripps Research Institute, senior author of the study. 'Your genome has to be stable for the scale of your lifetime. If the semi-synthetic organism is going to really be an organism, it has to be able to stably maintain that information.'

The new study, published in PNAS, builds on their previous work by modifying both the bacteria and the new bases so that the cells grow at a normal rate while retaining the modified DNA.

The researchers genetically modified a type of E. coli bacteria to improve their ability to absorb the X and Y bases. They also tweaked the chemical structure of the bases themselves. 

Finally, the researchers modified the CRISPR/Cas9 system in the E.coli genome so that if the synthetic bases were lost from the DNA, it would trigger a process of DNA degradation that led to cell death. Cells that retained the synthetic base pair were preferentially able to survive and reproduce.

'We can now get the light of life to stay on,' said Professor Romesberg, referring to the newfound stability of the semi-synthetic bacteria. 'That suggests that all of life's processes can be subject to manipulation.'

This work has no immediate practical application, but it is hoped it could lead to development of synthetic microbes for useful purposes, such as drug development. Currently, it stands as a proof of principle that it is possible to engineer life that uses synthetic chemicals and systems. This means that such organisms will not be able to survive except under controlled conditions.

Next, the researchers will study if their new genetic code can be transcribed into RNA, and eventually proteins.

'This will blow open what we can do with proteins,' Professor Romesberg told The Guardian.