04 June 2021

Synthetic E. coli

Scientists have created cells with an artificial genome resistant to viruses

RIA News

British scientists have reprogrammed the genome of E. coli bacteria, thus obtaining the first living cells with an artificial genome that can create polymers from building blocks that do not occur in nature, following the instructions embedded in their genes. In addition, they are not susceptible to any viruses.

The results of the study are published in the journal Science (Robertson et al., Sense codon reassignment enables viral resistance and encoded polymer synthesis).

In 2019, scientists from the Laboratory of Molecular Biology of the Medical Research Council Cambridge University, using its own method, created from scratch the largest synthetic genome in history – a genetically modified bacterium Escherichia coli (E.coli).

The genetic code encoded in DNA consists of four bases represented by letters: A, T, C and G. Three-letter combinations called codons, when assembled, instruct the cell to add a certain amino acid to the chain, which it does with the help of molecules called tRNA (transport RNA). Each codon has a specific tRNA that recognizes it and adds the corresponding amino acid: for example, the tRNA that recognizes the TCG codon brings the amino acid serine.

But four letters have 64 variants of three-letter combinations, and cells use only 20 natural amino acids in their construction. As a result, for each amino acid there are several codons-synonyms that duplicate each other. For example, serine is encoded by the codons TCG, TCA, AGC and AGT. Even if one of them does not turn out, the cell will still continue to assemble in accordance with the genetic code.

Experimentally, the researchers were convinced that cells can produce normal proteins, live and grow, even if three codons out of four are removed. Then the authors completely "rewrote" the E.coli genome, significantly simplifying it and removing all codons-synonyms. This made E. coli cells completely immune to viruses, since viruses use the full genetic code, and modified bacteria do not have a tool for reading certain viral genes.

In many biotechnologies, bacteria are used as living factories to create synthetic polymers – large molecules consisting of many repeating units. One of the varieties of polymers are proteins that are widely used in the production of many drugs, such as insulin, vaccines based on polysaccharides and protein subunits, as well as some antibiotics. According to the authors, increasing the resistance of bacteria with a synthetic genome to viruses will make the production of certain types of drugs more reliable and cheaper.

"If the virus gets into a bioreactor with bacteria used to produce certain drugs, it can destroy the entire batch. Our modified bacterial cells can solve this problem by being completely resistant to viruses," the press release says. The words of the British Committee for Research and Innovation (UKRI), the head of the project, Professor Jason Chin (Jason Chin).

The scientists' goal was also to use their new technology to create the first cell that can assemble polymers entirely from building blocks that are not found in nature. The ability to generate designer proteins and plastics using non-natural building blocks will open up countless applications, from the development of new classes of biotherapeutic agents to biomaterials with innovative properties, scientists believe.

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