Scientists Rewrite the Genetic Code of E. Coli, and It’s Drastically Different From Anything Found in Nature

The synthetic bacteria contain a shorter genetic code with 57 codons rather than 64, freeing up space for further edits that might lead to new drugs or virus-resistant microbes

Sara Hashemi | Daily Correspondent

August 7, 2025

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The DNA of nearly all life on Earth is made up of 64 codons, each one a sequence of three nucleotide bases, the building blocks of DNA. These codons contain instructions for building amino acids, which, in turn, combine to form proteins. But having so many codons is redundant—cells use only 20 amino acids, so some of them end up being coded for multiple times.

That’s why scientists have been working to “free up” codons from microbes, or remove them and shorten the genetic code. They hope to one day repurpose some of these sequences so that, instead of encoding amino acids that are already accounted for, they might code for other amino acids that don’t occur naturally. This could make the microbes produce new molecules that might lead to useful drugs or materials. It might even make the microbes virus-resistant.

Now, scientists have redesigned the genetic code of the bacterium Escherichia coli to contain just 57 of the 64 codons. The findings were published in late July in Science.

“This was a gargantuan effort,” lead author Wesley Robertson, a synthetic biologist at the Medical Research Council Laboratory of Molecular Biology in England, tells New Scientist’s Michael Le Page.

To do this, the researchers built the bacterium’s entire genome from scratch. Then, they started testing small, edited fragments of the DNA in living bacteria to determine which changes were okay to make and which ones did harm.

The work entailed lots of trial and error over the span of four years. “We definitely went through these periods where we were like, ‘Well, will this be a dead end, or can we see this through?’” Robertson recalls to Carl Zimmer at the New York Times. The team had to invent repairs along the way to undo the damage.

DNA is made up of four nucleotide bases, or letters, that form the building blocks of genetic code: adenine (A), thymine (T), guanine (G) and cytosine (C). These bases, in various combinations of three, make the 64 codons—61 that code for amino acids and three stop codons that send messages to end protein synthesis.

Because cells have 20 amino acids available to form proteins, a living organism should technically only need 21 codons: one for each amino acid and one stop codon. Scientists don’t know if the redundant codons serve a purpose. But within an entire molecule of DNA, a single type of codon could appear thousands of times—so freeing up even one requires lots of painstaking edits.

In 2019, researchers made synthetic E. coli bacteria called Syn61, with only 61 codons rather than 64. That process took 18,000 changes to the microbe’s letters of DNA. This time, Robertson and his colleagues made more than 100,000 changes to the DNA, producing the 57-codon bacteria, called Syn57.

“It’s a radically recoded genome,” Robertson tells Elizabeth Walsh at Chemical & Engineering News.

“This is a significant achievement and the result of years of work,” adds Akos Nyerges, a synthetic biologist at Harvard Medical School working on similar research, to New Scientist. His team is working on shrinking the genome of E. coli by freeing up different codons than Robertson’s team. “Our 57-codon E. coli strain is still in progress,” Nyerges adds.

Currently, Syn57 grows four times slower than normal E. coli, but the researchers expect that with further research they can accelerate its growing speed. With additional edits, it might have key uses in biotechnology and commercial applications. Since its debut in 2019, Syn61 is already being used to manufacture more reliable drugs, writes Phys.org’s Krystal Kasal.

“This work exemplifies how genome synthesis can move the genome sequences of organisms into new regions of sequence space that may not have been accessed by natural life,” the authors write in the paper.

Meanwhile, Nyerges and his team are also getting close to their version of Syn57—they have created a 57-codon genome, but it’s broken into seven disconnected pieces of DNA, reports the New York Times. They’re now working on stitching everything together into one molecule. “We will definitely get there,” he tells the outlet.

Sara Hashemi | Read More

Sara Hashemi is a science writer and fact-checker currently based in New York City. Her work has appeared in Sierra, The Body, Maisonneuve magazine and more.