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Synthetic E. coli reprogramed with multiple new genetic building blocks exhibit viral resistance

2021-06-03
(Press-News.org) By engineering the genetic code of a synthetic strain of E. coli to include several nonstandard amino acids, researchers rendered the synthetic bacterium virtually invincible to viral infection. Their work is some of the first to design proteins using not one but multiple non-canonical amino acids. "The ability to generate designer proteins using multiple non-natural building blocks will unlock countless applications, from the development of new classes of biotherapeutics to biomaterials with innovative properties," write Delila Jewel and Abhishek Chatterjee in a related Perspective. In nature, biological systems use 64 codons - a unique triplet of nucleotides - to encode and guide the templated synthesis of proteins from a collection of 20 canonical amino acid building blocks. It's thought that removing certain codons and the transfer RNAs that read them from the genome and replacing them with noncanonical amino acids (ncAAs) may enable the creation of synthetic cells with properties not found in natural biology, including powerful viral resistances and enhanced biosynthesis of novel proteins. However, while hundreds of different ncAAs have been genetically encoded in various domains of life, the approach has been largely restricted to the incorporation of a single ncAA into a polypeptide chain. Here, Wesley Robertson and colleagues demonstrate site-specific incorporation of multiple distinct ncAAs into proteins using a synthetic strain of E. coli. Robertson et al. deleted transfer RNAs and release factor1 and created E. coli cells that do not read several codons. Because viruses rely on the host cell's ability to read all the codons in the viral genome to reproduce, the modified E. coli cells became completely resistant to a wide variety of viruses. What's more, the authors reassigned each of these codons to three distinct ncAAs and show that the efficient synthesis of designer proteins is, indeed, possible.

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[Press-News.org] Synthetic E. coli reprogramed with multiple new genetic building blocks exhibit viral resistance