Scientists have successfully produced Escheria coli bacteria in the laboratory entirely made up of synthetic DNA, according to a new study published on 15 May in Nature (1).
Synthetic DNA has been created prior to this. The most notable examples are Baker’s yeast or Saccharomyces cerevisiae and the bacterium Mycoplasma mycoides. But those genomes only contained up to one million base pairs. With 4-million base pairs, the E.coli genome is the largest, to date, to be created entirely from scratch – four times larger and far more complex. The study is being hailed a landmark achievement in synthetic biology.
‘Recoding’ the genome
To recode the E. coli genome with entirely synthetic DNA, the scientists, led by Dr Jason Chin from the Medical Research Council Laboratory of Molecular Biology at the University of Cambridge in the UK first had the task of manipulating the 64 codons at their disposal.
Codons are three-letter DNA combinations — A, T, C, or G, shorthand for adenine, thymine, cytosine, and guanine — that either specify a particular amino acid sequence to build a protein or a stop signal. These proteins are crucial since they allow cells to perform many of the functions necessary for life. Since a single codon can hold three of a possible four letters, that means there are 4x4x4 or 64 combinations.
However, nature has built in some redundancies. Since there are just 20 amino acids, a single amino acid may be associated with more than one codon, although some codons are also used as ‘stop’ codes, which tell cells to stop producing a particular amino acid.
What this essentially means is that there are numerous ways to rebuild the genome. But what is the reason for all the redundancies? And is all of this extra DNA really needed? Indeed, not all of the possible combinations can keep the cells alive. So, to figure out the possible combinations, the researchers used a “search-and-replace function”.
Once the synthetic genome was established, the next step was inserting the genetic code into cells. This was done by breaking the genome into pieces and introducing it step-by-step – an incredibly tedious process. Slowly, all the DNA segments were replaced and no natural segments were left in the bacteria.
The new bacterium called Syn61 contains only 61 codons compared to the 64 found in nearly all living organisms yet still seems to function like normal E. coli – with the exception of a slower growth rate and longer length. Importantly, the cells are still capable of producing the same proteins but using a different genetic code.
What are the possible implications?
The breakthrough paves the way for paving the way for developing many more of these “designer” bacteria.
Bacteria like E. coli are already being used as pharmaceutical production factories to make insulin and other medical compounds to treat cancers and various diseases. The new findings could pave the way toward new molecules, vitamins, or even vaccines.
Another possibility is that viruses may not be able to invade recoded cells, paving the way for potential anti-viral treatments. Or engineering cells with genes that don’t work if they invade other species.
Finally, the remaining three unused codons offer the potential to reprogramme the bacteria to perform previously unimaginable functions. The possibilities could be endless.
(1) Fredens, J. et al. Total synthesis of Escherichia coli with a recoded genome. Nature (2019). DOI: 10.1038/s41586-019-1192-5