Researchers at the Cambridge Medical Research Council (UK) they have created, by genetic engineering, a synthetic strain of E. coli in which they included several non-standard amino acids. In this way, they got the synthetic bacteria was protected from viral infection.
Their work, published this week in the journal ‘Science’, is one of the first to design proteins using not one but several non-canonical amino acids (ncAA), that is, hundreds of molecules that can be found in nature or in the laboratory but that organisms do not innately use.
The authors genetically engineered a synthetic strain of E. coli in which they included several non-standard amino acids. In this way, they managed to protect the synthetic bacteria from viral infection. “The ability to generate designer proteins using multiple unnatural ‘building blocks’ will unlock myriad applications, from the development of new biotherapies to biomaterials with innovative propertiesDelila Jewel and Abhishek Chatterjee write in a related article.
For us to understand each other, in nature biological systems use 64 codons – each of them is a sequence of three nucleotides of DNA or RNA that corresponds to a specific amino acid – to encode protein synthesis. However, there are 64 different triplets and there are only 20 different canonical or natural amino acids, so different codons determine the same amino acid. This is called degeneration of the genetic code.
Experts believe that removing certain codons and the transfer RNAs that read them from the genome, and replacing them with amino acids ncAA, may allow the creation of synthetic cells with properties not found in biology, such as powerful viral resistance and increased biosynthesis of new proteins. However, although hundreds of different ncAAs have been genetically encoded in various walks of life, until now the focus has been largely limited to incorporating a single non-canonical amino acid into a peptide.
Unbeatable bacteria against viral infections
The new Science work demonstrates how specific incorporation of multiple different ncAAs into proteins is possible using a synthetic strain of E. coli. Thus, a team led by Jason Chin eliminated transfer RNAs and release factor 1 and created cells of this bacterium that do not read several codons. Therefore, as viruses depend on the capacity of the host cell In order to read all the codons of the viral genome to reproduce, the modified E. coli cells became completely resistant to a wide variety of viruses.
The Cambridge specialists reassigned each of these codons to three different ncAAs and showed that “efficient synthesis of designer proteins is indeed possible.”