Scientists Have Just Created The Most Synthetic Life Form Ever

Scientists have produced a bacterial strain with a genetic code that is both more pared-back - and more heavily reworked - than anything else known on Earth.

Syn57: a synthetic Escherichia coli with a 57-codon genetic code

The microbe is a synthetic Escherichia coli known as Syn57, designed to build itself using only 57 of the 64 “codons” that every known organism has relied upon for billions of years.

Life’s instructions are written in a system of 64 distinct codons, each made from a three-nucleotide sequence. Our DNA and RNA are, in effect, long strings of these three-letter codons.

Those strings give cells the critical directions needed to turn ordinary matter into the components of life: amino acids, which are linked in order to make proteins. When a cell manufactures proteins, it “reads” the codon sequence - built from those 64 nucleotide triplets - to determine which amino acid to add next and when to stop.

Yet the code contains puzzling repetition. All natural organisms can make the proteins they require using just 20 amino acids, which means many codons are effectively synonymous duplicates.

Syn57 removes some of these apparently unnecessary codons. Other groups have pursued the same objective, but a team at the Medical Research Council Laboratory of Molecular Biology in the UK is the first to reduce a living system to the 57-codon threshold, beating the earlier milestone of a 61-codon genome.

To do this, the researchers built the entire genome from the ground up. Their plan was to eliminate four of the six codons linked to the amino acid serine, two of the four alanine codons, and one “stop” codon. Wherever these redundant codons occurred in the bacterium’s genome, they replaced them with synonymous codons that carry the same meaning.

In total, the redesign demanded more than 101,000 edits to the genetic code. The changes were mapped first in software, broken into 100-kilobyte sections, and only then did the painstaking work begin to physically assemble the genome.

To ensure the edits were not introducing changes that would be fundamentally damaging, the team evaluated small portions of the synthetic genome inside living bacteria, step by step, before ultimately joining everything together into the final, fully synthetic strain.

"We definitely went through these periods where we were like, 'Well, will this be a dead end, or can we see this through?'" synthetic biologist Wesley Robertson, one of the study's lead authors, told New York Times journalist Carl Zimmer.

The scale of the effort demonstrates that life can persist with a markedly compressed genetic blueprint. It may also open up the remaining codons so they can be reassigned to new functions.

"Syn57 has more space to introduce further non-canonical amino acids, presenting greater opportunities to expand the genetic code even further," the team says in a press release. "This will allow researchers to develop innovative synthetic polymers and macrocycles."

Because Syn57’s “non-canonical” genetic code ought to be unreadable to “natural” microbes such as viruses - which typically hijack a cell’s protein-making machinery - the bacterium should be better able to withstand infection. That, in turn, could cut costs in industrial “farming” of bacterial proteins, where viral outbreaks can be a major setback.

A genome that other organisms cannot interpret could also act as an effective form of sterilisation for genetically modified bacteria, which may help address worries about altered genes leaking into the wider environment.

"We can then prevent the escape of information from our synthetic organism," Robertson told Zimmer.

"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 team concludes.

This research was published in Science.