Synthetic biology is quickly moving towards a future where genomes can be engineered-to-order, with researchers using this discipline to better define the minimal set of genes required for a living artificial cell to carry out desired functions. Recently researchers have scaled up synthetic biology to generating entire chromosomes and genomes. Now, a study from researchers at University Cambridge develops living artificial life using the bacteria Escherichia coli and human DNA, synthesized to contain a smaller set of amino-acid-encoding codons than usual. The team states their construction of the biggest synthetic genome so far at four million base pairs long, raises the prospect of encoding proteins containing unnatural amino-acid residues. The opensource study is published in the journal Nature.
Previous studies show genetic code is written in four letters, namely, A, T, C, and G, which represent the molecules adenine, thymine, cytosine, and guanine. These nucleotides can arrange into 64, three-letter ‘codons,’ to encode just 20 amino acids plus the ‘start’ and ‘stop’ points marking the beginning and end of a stretch of the protein-coding sequence. The current study rewrites the DNA of Escherichia coli, demonstrating the number of codons used to encode amino acids can be reduced through the genome-wide substitution of target codons by defined synonyms, codons which are spelled differently and give the same instruction.
The current study designs a genome where two codons and the stop codon are replaced which encode the amino acid serine with synonyms. The synthetic DNA was then built and used to replace the Escherichia Coli’s genetic material by breaking the artificial genome into pieces, and slowly transplanting it bit by bit into living bacteria until the entire Escherichia Coli genome was replaced. Results show the Escherichia coli survived, though they grew slower and were longer; however, the new Escherichia coli cells relied on only 61, rather than 64 total codons.
Data findings show the synthetic genome implements a defined recoding and refactoring scheme, with simple corrections at just seven positions, to replace every known occurrence of two sense codons and a stop codon in the genome. Results show 18,214 codons were successfully recoded to create an organism with a 61-codon genome; this organism uses 59 codons to encode the 20 amino acids and enables the deletion of a previously essential transfer RNA. The team states the altered E. coli is alive, grows slower than regular E. coli and develop longer rod-shaped cells.
The team surmises they have constructed artificial living organisms made out of minimized human-made DNA. For the future, the researchers state removing the redundancies means there are extra codons to experiment with, potentially developing new amino acids, proteins, and bacteria.
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