UK researchers have created an artificial version of the E. coli stomach based on a completely synthetic form of DNA.
While Syn61 as they call it has got its genetic code significantly redesigned.
It has been done in a way that will pave the way for designer bacteria that can produce new catalysts, drugs, proteins and materials.
Other researchers working in synthetic biology have praised the development.
Genetic engineer, Prof George Church, from Harvard University, USA, has hailed the work as a "great crime".
Dr. Tom Ellis, a reader of synthetic biology at Imperial College London called it super interesting.
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Syn61's 4 million genetic letters make this the largest whole genome to be synthesized from the beginning.
They were ordered in short segments from a laboratory supply company before being mounted in half million letter lengths in yeast cells of natural cellular machinery.
On this occasion, the engineers' jobs became a bit like a railway engineer maintenance program – replacing the E. coli genome in section – rather than at once.
"The bacterial chromosome is so great," said team leader Jason Chin to the BBC: "We needed an approach that would let us see what went wrong if there were any mistakes along the way."
So it was only after every half a million letter segments had been tested in partially synthetic bacteria that the eight segments were collected in Syn61.
The approach is more cautious than that used by bio instructor Craig Venter, whose microbial replica was based on the small organism Mycoplasma genitalium was presented to the world in 2010.
It was a milestone, Tells Tom Ellis, but consumes the efforts for many years by an entire institute, established, driven and named by Venter.
The new work was done by a small team in Cambridge's world-renowned molecular biology laboratory and could easily be scaled up to larger genomes in any well-equipped lab, according to Dr. Chin.
In the event that Team found just four mistakes out of the four million synthesized genetic letters, they were easily corrected.
But Dr. Chin's ambitions go far beyond record breaking chromosomes.
The new genome has also been re-encoded, as a first step that allows the synthetic biologists to integrate components into biomolecules that do not exist in nature.
The code on DNA carries instructions for the cell for how to assemble proteins, primary biomolecules in a body.
Just as DNA consists of strands of simple nucleic acid elements, proteins are made of strands of single amino acids.
Nature has a palette of 20, with names such as serine, leucine and alanine. Their chemistry dictates the properties of the protein they make – from hair to muscle proteins, to gastric enzymes.
But even though nature is dependent on only 20, the DNA code can accommodate up to 64. DNA biologist Francis Crick, who worked at LMB in his early days, called this a frozen accident. As a result, many of the DNAs direct the "words" or the codons to the same amino acid. There are six ways, for example, to write the instructions for serine – which Chin sees as wasteful.
"We have removed some of the duplicates in the natural code to make it more effective," said his colleague Julius Fredens, who oversaw much of the detailed lab work.
They decided to find all occurrences of two variants of the serine instruction and replace them synthetically with two of the other synonyms – a large-scale task to find all "C's and Q's" in the Bible and replace them with "K" so that "fast" becomes "mercury".
The team also reduced the number of codons (as full stop) marking the ends of genes from three to two. There were over 18,000 allowances in all.
"This was a real radical transformation," Chin says.
There were further changes to remove the cellular machine reading the lost codons – it was no longer needed. [Impressive] Syn61 does not appear to be as powerful as its natural E. coli cousin – it grows about 60% slower. Although it might suggest that there may be some essentials about the alternate spelling of the genetic code, Julius Fredens believes that they have identified minor problems in Syn61, which should be corrected to fully restore the health of the organism.
Tom Ellis is impressed by the bacteria working at all and says: "These 18,000 changes mean that every gene on the chromosome will have changed – and yet it still lives!"
An effect of the recoden is that it separates Syn61 from all other life. So far, organisms have been able to change genes, often via viruses, since they all share the same basic language. Now, a virus trying to infect Syn61 finds that the host cell lacks the tools to translate viral DNA; the attempt would fail.
George Church calls this "cliffhanger". In a previous experiment in his lab, with a limited set of edits, one in five viruses still managed to replicate.
"Chin's success will embrace the rest of us who work to make many organisms (industrial microbes, plants, animals and human cells) resistant to all viruses by this encoding," the church wrote in an email.
Chin says that test has not been tested than with Syn61, but it is high on its to do list.
But Chin's big plan is to make the biochemistry more versatile.
With only 61 of Syn61's 64 possible codons listed as instructions for natural amino acids (hence the name), three that can now be redistributed leave unnatural that could introduce entirely new chemistry into the cell.
Chin has pioneered this type of synthetic biology that introduces elements that make proteins glowing or respond to light by becoming active or shut down.
Fredens considered that there are already 200 unnatural building blocks that could be put into protein chemistry in this way, and that these would work with techniques that have already been developed at LMB and elsewhere.
"It's pretty quiet that you can expand the genetic alphabet in this way, admits Fredens." I think we are quite far from realizing how much we can do with it and produce things that we have never seen before. "
Chin focuses heavily on what the opportunities will do for science, talks about alternative proteins that will spy on the inner effects of the cells or help drug companies build better drugs. But the possibilities are endless. Tom Ellis speculates on the idea of linking molecular hooks on proteins that would allow them to click together to make large molecular networks in smart materials.
It may sound like a brave new molecular world, but Chin says it shouldn't be scary.
"People have legitimate worries, "he accepts." It is twice the use of everything we invent. But what is important is that we have a debate about what we should and should not do. And that these experiments are done in a well-controlled manner. "