Expanding DNA's alphabet lets cells produce novel proteins

Expanding DNA's alphabet lets cells produce novel proteins
This undated photo provided by The Scripps Research Institute shows a semi-synthetic strain of E. coli bacteria that can churn out novel proteins. Scientists reported on Wednesday, Nov. 29, 2017, that they have expanded the genetic code of life and used man-made DNA to create this strain of bacteria. (Bill Kiosses/The Scripps Research Institute via AP)

Scientists are expanding the genetic code of life, using man-made DNA to create a semi-synthetic strain of bacteria—and new research shows those altered microbes actually worked to produce proteins unlike those found in nature.

It's a step toward designer drug development.

One of the first lessons in high school biology: All life is made up of four DNA building blocks known by the letters A, T, C and G. Paired together, they form DNA's ladder-like rungs. Now there's a new rung on that ladder.

A team at The Scripps Research Institute in La Jolla, California, expanded the genetic alphabet, creating two artificial DNA "letters" called X and Y. A few years ago, the researchers brewed up a type of E. coli bacteria commonly used for lab research that contained both natural DNA and this new artificial base pair—storing extra genetic information inside cells.

The next challenge: Normal DNA contains the coding for cells to form proteins that do the work of life. Could cells carrying this weird genomic hybrid work the same way?

Sure enough, the altered cells glowed green as they produced a fluorescent containing , researchers reported Wednesday in the journal Nature.

"We can make proteins that are built of more things than they normally are," explained Scripps chemist Floyd Romesberg, who leads the project.

Expanding DNA's alphabet lets cells produce novel proteins
Schematic depicting the incorporation of a non-canonical amino acid (ncAA) into a protein via ribosomal decoding of an unnatural codon in a semi-synthetic organism Credit: Adapted from an image created by Dennis Sun, Mezarque Design

While programming the green germs offered evidence that the approach can work, eventually "we would like to get proteins that do new things," he said.

That's an ultimate goal in the field of synthetic biology—designing organisms that work differently from the way nature intended so scientists can harness them to create designer drugs, biofuels or a range of other products. Scripps' technology has been licensed by a biotech company Romesberg co-founded, Synthorx Inc., that aims to make novel protein-based drugs.

The new work traced the biological steps as the altered E. coli read the artificial and assembled the pieces for a new protein, with the same efficiency as if using normal DNA.

The result is a platform that offers a way to increase the diversity of proteins made inside living , said Jef Boeke, a synthetic biology researcher at New York University who wasn't involved in Scripps' work.

Expanding DNA's alphabet lets cells produce novel proteins
Semi-synthetic organism (E. coli) producing green fluorescent protein via decoding of an unnatural codon Credit: William B. Kiosses

This bacterial strain was "modified in a really dramatic and unusual way at these positions in its genome," Boeke said. "And that's what makes it different from every other organism on the planet today."


Explore further

Scientists create first stable semisynthetic organism

More information: Yorke Zhang et al. A semi-synthetic organism that stores and retrieves increased genetic information, Nature (2017). DOI: 10.1038/nature24659
Journal information: Nature

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Nov 29, 2017
I wonder what these artificial DNA compounds will do within human cells, or those of other life forms? It's a matter of when, not if, they get loose into the biosphere. Pandemics? Beneficial evolution? Perhaps both. We're going to find out, sooner or later.

Nov 29, 2017
Z Still Remains for now.
Later on - B, D upto F, H UPTO S and U upto W !
Total of 20 LETTERS Left Out !
When, When, When ???
Hurry up, Please. Immense Opportunity AWAITS for Humanity !
AS GOOD AS Quantum Computer to Supersede Super Computer, WoW !
Change a Mouse with this, Not a Bacterium.

Nov 29, 2017
Scientists designed part of X and Y to be hydrophobic—so that they only pair with each other and repel the usual hydrogen bonding natural bases, which keeps X and Y from accidentally pairing with A, T, C or G. It turns out that a lack of complementary hydrogen bonds doesn't really bother cells. As the scientists found, X and Y were successfully transcribed and translated anyway."What is remarkable about our findings is not just the fact that the cells are able to transcribe and translate these hydrophobic unnatural bases, but that they do so very efficiently," said TSRI Graduate Student Yorke Zhang, first author of the study. "We were able to achieve purities of desired amino acid incorporation above 98 percent, which demonstrates how seamlessly our synthetic bases can be integrated into the natural processes for encoding and decoding genetic information."

Nov 29, 2017
I wonder what these artificial DNA compounds will do within human cells, or those of other life forms? It's a matter of when, not if, they get loose into the biosphere. Pandemics? Beneficial evolution? Perhaps both. We're going to find out, sooner or later.

Scientists added that it is impossible for this semi-synthetic organism to live outside the lab, as no lifeform can produce its own X and Y without scientists adding the right chemicals.

Nov 30, 2017
hugely over hyped implications. At this time, they have just achieved the equivalent of changing color of a car in terms of complexity. Surely, the company is over hyping its business. Which is all about introducing a few unconventional aminoacids in antibodies to conjugate with drug molecules. This is already achieved with conventional biology. The good thing (for them) is that such "innovative" version gives them an ironclad patent being not existing in nature. Regardless any actual improvement in the production, safety, efficacy of the biotherapeutics

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