All life on Earth is underpinned by the same DNA building blocks. DNA consists of pairs of four biological compounds known as nucleobases – A, T, C, G (Adenine, Cytosine, Thymine, and Guanine). But what if we created new artificial nucelobases to add to those pairs? Researchers at The Scripps Research Institute are now finding out, having successfully created a semi-synthetic bacteria strain with two new unnatural bases.
For several years, the research team has worked on creating a stable, living organism with new, unnatural DNA base pairs. The synthetic bases, dubbed "X" and "Y", were added into the DNA of a strain of E. coli bacteria.
Earlier in 2017, the team revealed that after several unsuccessful attempts, it had finally stabilized the semi-synthetic bacteria, and got it to grow and divide naturally, passing on the synthetic "X" and "Y" bases to new generations. The next step was to get this organism to generate a novel molecule using its new synthetic bases.
All organisms generate proteins from strings of amino acids using the standard four "letters" of the DNA alphabet. Life as we know it is underpinned by 20 standard amino acids, but this new research reveals that by adding two new "letters" to the DNA alphabet an organism could conceivably generate up to 152 new amino acids.
What this means is that entirely new molecules may be created that could hypothetically become the foundation for new medicines.
And now the creation of a completely new and unnatural protein has been effectively demonstrated with the semi-synthetic organism expressing a variant of green fluorescent protein. These naturally glowing protein markers are the first artificial molecules ever produced by a semi-synthetic organism.
"This was the smallest possible change we could make to the way life works – but it is the first ever," says study lead, Floyd Romesberg.
The implications of this breakthrough are hard to fathom. While current genetic engineering techniques are experimenting with altering the expression of existing genes, this new innovation is like generating an entirely new language. In the future this could allow scientists to build entirely alien molecules that can do in the human body whatever we ask them to.
Romesberg is not unaware of these implications and has founded a company called Synthorx with the goal of developing new protein therapeutics from the technology. Synthorx's CEO is already pushing to move the work into clinical applications.
The study was published in the journal Nature.
Source: The Scripps Research Institute