"We can fit another stop codon over here next to the kitchen."

Yes, their creators call the Genomically Recoded Organisms they madeGROs. But they are not quite as menacing as they sound.

Genetic engineering had, until Y2K at least, was not exactly what it sounds like. No one was really engineering completely new genes that encoded completely new proteins that generated completely new life forms. But the newest generation of tinkerers thought: why not?

The genetic code that is used universally by all life on Earthgiant sequoias, daddy long legs, bakers yeast, barracudas, ring tailed lemurs, you get the idea. It dictates that specific amino acids are encoded by specific combinations of three nucleotide DNA sequences, called codons.

These tinkerers decided that this doesn't need to limit us. And ,just because this genetic code, and the entire variety of life defined by it uses only twenty amino acids; again, why should we? The researchers' attempt to work around these limits is reported in this weeks Science. These upstarts, led by Farren Isaacs at Yale but including people at Harvard, MIT, Columbia, and the Scripps Research Institute, decided to alter the genetic code and generate proteins with nonstandard amino acids.

Why would they do such a thing? The fact that all organisms share a genetic code means we can share genes, which can be good or bad. Notably, viruses hijack cellular machinery so whatever cell they are infecting makes viral proteins instead of what the cell itself needs; GROs might not have this problem. And there are those that are concerned about genetically modified organisms (GMOs) releasing DNA into the environment; if these were genomically recoded in addition to being genetically modified (GRO-GMOs?) this should pose less of a risk.

You might think that they'd start small, with a virus. But this is the super cool part: the organism they genomically recoded is a bacterium, a strain of Escherichia coli. Like all other life forms, E. coli uses three distinct stop codons to signal a halt to protein production. These researchers changed all the instances of one of these stop codons (UAG) into another, AUG. (We've covered the technology that enables this.) This enabled them to get rid of the cellular machinery that recognizes the UAG as a signal to stop making proteins.

Once that was eliminated, they reinserted UAG codons along with new machinery that recognized it as a regular codon, encoding a particular amino acidonly a nonstandard one not used by or found in any other life form. They reassigned a codon to create an alternate genetic code. Nifty right?

This GRO grew even more efficiently than the strain form which it was generated, and it exhibited significantly enhanced resistance to T7 bacteriophage, probably because it would mistranslate any viral proteins containing UAG codons. Oops from the virus' perspective, but good for the bacteria.

The authors note that they have identified an additional twelve codons that may be amenable to removal and eventual reassignment in E. coli, helping them achieve their goal of incorporating nonstandard amino acids that expand the chemical diversity of proteins in vivo. Whether or not they enhance virus resistance, the whole genomic recoding thing is cool as hell.

Go here to read the rest:
Meet the genomically recoded organisms

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