Microbe Engineered With Semi-Synthetic DNA Can Make Proteins Not Found In Nature


All life that we know contains four DNA bases, now researchers have managed to insert two new ones. ktsdesign/Shutterstock

For billions of years, life has been growing, reproducing, and evolving using an amazingly limited palette. Utilizing just four different codes in its genetic material, it has managed to form everything from the mighty redwood tree to the smallest shrimp.

Now this system has been given an incredible shakeup, as bacteria have been engineered not only to contain two extra base pairs, but to read these additions and create novel proteins as a result. The work is published in Nature


All natural life is founded on the genetic code held in (almost) every cell. It's constructed from four base pairs that we call A, T, G, and C. With just these few bases, the cell can create all the different proteins needed to construct life. The researchers, however, have managed to create and insert two entire synthetic base pairs into a microbe's genetic code, which they have called X and Y.

This moment has been years in the making for the researchers at The Scripps Research Institute. It was initially announced in 2014 that the team had managed to create an engineered strain of E. coli with this expanded DNA, but the microbes were unstable and kept kicking out their extra base pairs when they divided.

It would take another three years for them to finally perfect the technique that made the bacteria’s DNA durable enough for the extra pair of genetic bases to be passed on. Revealing their progress in January this year, they detailed how they had managed this in a three-pronged attack, but the most crucial step involved tinkering with the microbe’s immune system so that when it divided, it would destroy any DNA that did not contain the two synthetic bases.   

But while this meant that the bacteria could theoretically grow and divide indefinitely (the organisms require the scientists to feed them the synthetic bases, a failsafe should the microbes escape), they were still just short of that final step of reading the code and translating it into protein.


Quite astonishingly, it seems that this final hurdle has been overcome.  

The team has reported that the engineered microbes can now read their six-base-pair DNA and turn it into proteins that don't exist in nature. The cells have initially been programmed to insert unnatural amino acids into a fluorescent protein, but it is thought that such an achievement could be monumental in the development of new drugs.

If this can be replicated and shown to be stable, it will completely alter how work is done with proteins, as in principle at least, scientists will no longer be constrained by what is found naturally. One of the biggest applications could be within the medical field, creating new protein-based drugs.


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