Saturday, April 01, 2023

New Synthetic E. coli Is Immune to Bacteriophage Infection

Good news! Welcome to the age of synthetic organisms!

"... Now, in a study published in Nature on March 15, researchers from Harvard Medical School report a new E. coli strain that can resist viral infections but is unable to release its modified genes in the wild, reducing the risk of incorporating the modified genetic material into natural cells.
To create the new E. coli strain, dubbed Ec_Syn61?3-SL, the team started with the synthetic bacterium Syn61?3, generated by UK researchers in 2021, which has a reduced number of codons—the three-nucleotide sequences in DNA that correspond to a particular amino acid. Instead of the naturally occurring 64 sets, it only has 61, as three specific codons were excluded from its genome: two encoding for the amino acid serine and the other instructing protein assembly to stop. Furthermore, the UK team also removed from the bacterial genome the transfer RNA (tRNA) molecules that correspond to those codons. Since tRNAs are responsible for incorporating amino acids into a growing protein chain, bacteriophages that infected the reduced-codon bacteria would find its cellular machinery defective and unable to sustain viral replication, whereases the bacteria could still use the 61 codon sets to produce all the proteins it needed to live. ..."

From the abstract:
"Engineering the genetic code of an organism has been proposed to provide a firewall from natural ecosystems by preventing viral infections and gene transfer. However, numerous viruses and mobile genetic elements encode parts of the translational apparatus, potentially rendering a genetic-code-based firewall ineffective. Here we show that such mobile transfer RNAs (tRNAs) enable gene transfer and allow viral replication in Escherichia coli despite the genome-wide removal of 3 of the 64 codons and the previously essential cognate tRNA and release factor genes. We then establish a genetic firewall by discovering viral tRNAs that provide exceptionally efficient codon reassignment allowing us to develop cells bearing an amino acid-swapped genetic code that reassigns two of the six serine codons to leucine during translation. This amino acid-swapped genetic code renders cells resistant to viral infections by mistranslating viral proteomes and prevents the escape of synthetic genetic information by engineered reliance on serine codons to produce leucine-requiring proteins. As these cells may have a selective advantage over wild organisms due to virus resistance, we also repurpose a third codon to biocontain this virus-resistant host through dependence on an amino acid not found in nature. Our results may provide the basis for a general strategy to make any organism safely resistant to all natural viruses and prevent genetic information flow into and out of genetically modified organisms."

New Synthetic E. coli Is Immune to Bacteriophage Infection | The Scientist Magazine®

A swapped genetic code prevents viral infections and gene transfer (no public access, but article above contains link to PDF)



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