E. coli created with world’s first synthetic and redesigned genome

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Scientists have created the world’s first living organism that has a synthetic and altered genetic code. This research could provide opportunities for organisms whose biological machinery is commandeered to make drugs and useful materials, or to add new features such as virus resistance.

The organism consists of the bacteria Escherichia coli that has been radically redesigned to survive on a smaller set of codons. Prior to this work, in 2010, US scientists had announced the creation of the world’s first organism with a synthetic genome, Mycoplasma mycoides, however, this organism was much smaller than the recent E. coli at 1m base pairs, in addition, it was not redesigned.

The study, recently published in Nature, reports that the E. coli’s redesigned  genome consists of 4m base pairs using only 61 codons, as opposed to the naturally occurring 64. The team set out to condense E. coli’s genome by removing superfluous codons – reading the genome and replacing any instances of three codons where there were other codons that could do the same job. Specifically, instead of six codons encoding serine this genome used four, in addition, the genome consisted of only two stop codons, as opposed to three.

The project consisted of over 18,000 edits, after which the redesigned genome was chemically synthesized and added to E. coli, where it replaced the organism’s natural genome. The team observed that the modified E. coli, known as Syn61, was more elongated and grows more slowly compared with its natural counterpart, however, it was able to survive on an altered genome.

Organisms such as this could be used in the future to produce novel medicines or other molecules. The team hope to build on this experiment by removing more codons and compressing the genetic code further.

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Source: Fredens J, Wang K, de la Torre D et al. Total synthesis of Escherichia coli with a recoded genome. Nature doi:10.1038/s41586-019-1192-5 (2019).

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