A stable semi-synthetic bacterium created

Bacteria of the species Escherichia Coli seen wih an electronic microscope (Image Rocky Mountain Laboratories, NIAID, NIH)
Bacteria of the species Escherichia Coli seen wih an electronic microscope (Image Rocky Mountain Laboratories, NIAID, NIH)

An article published in the journal “Proceedings of the National Academy of Sciences” describes the creation of a semi-synthetic organism. A team at The Scripps Research Institute (TSRI) in La Jolla, California, led by Floyd Romesberg created a bacterium of the Escherichia coli family with a modified genome that contains two artificial nucleotides in addition to the four existing in the DNA.

DNA contains four bases: adenine, cytosine, guanine and thymine, also indicated by the four initial letters: A, C, G and T, which form all the genes of living organisms on Earth. TSRI Professor Floyd Romesberg has has been researching for years to figure out if he could create other pairs of working bases and in an article published in 2014 in the journal “Nature” described the results and the pair of synthetic bases called d5SICS and DNAM or simply X and Y.

That research had already created the first modified bacterium Escherichia coli with a semi-synthetic genome but it showed a number of limitations in its biological functions and could not keep the artificial bases. Working on those results, Floyd Romesberg’s team modified the X and Y bases so that they’d integrate stably into the bacterial DNA to obtain a semi-synthetic organism that can grow and reproduce normally.

During this new phase of the research, the scientists also used the CRISPR-Cas9 technique, the one that at the moment is probably the most popular genetic engineering technique, in an innovative way. This time this technique hasn’t been used to alter the bacterium’s genome but in a manner more similar to its purpose in nature, which is to protect bacteria from viruses. It’s in fact an enzyme that this time was used to eliminate the versions of the semi-synthetic bacterium in which the X and Y bases didn’t integrate well into the genome.

The surviving bacteria are those that maintained the synthetic bases in their genome. In the experiment, this semi-synthetic organism was able to divide for 60 times and each new generation has kept the bases X and Y in its genome. This led the scientists to think that it can replicate indefinitely and keep the artificial bases as a stable part of its genome.

This is a new phase of a long research conducted by Floyd Romesberg and his associates but it’s far from over because the synthetic bases do nothing. The next step will be to be able to use those bases to create proteins. This would allow to start designing new versions of bacteria capable of creating useful substances, for example medicinal products.

These searches are restricted to bacteria and Floyd Romesberg clarified that he won’t extend them to more complex organisms. Creating artificially mutated organisms always raises ethical questions but the research is far ahead in normal DNA manipulation while these one about the addition of synthetic bases will still take years before it’s necessary to make that kind of assessment.

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