Evolution settled on a genetic code that uses four letters to name 20 amino acids. Synthetic biologists adding new bases to DNA will be free to improve on nature — if they can.
Quanta Magazine said:With recent innovations in gene editing, it may seem as if the field of synthetic biology is just starting to make strides into science-fiction territory. But for several decades, scientists have been cultivating ways to create novel forms of life with basic biochemical components and properties far removed from anything found in nature. In particular, they’re working to expand the number of amino acids — the building blocks of the proteins that perform the cell’s functions — in life’s stockpile.
In November, a group of researchers announced some of their greatest progress yet. But that breakthrough has also provided the opportunity to reflect on how and why they are looking to improve on nature at all — and what challenges they may face in turning those successes into more than demonstrations. A long history of theoretical work, after all, suggests that natural evolutionary forces settled on the genetic code universal to most organisms for good reason.
The impetus to engineer a more extensive code comes with several long-term goals. With more amino acids, it becomes possible to synthesize artificial proteins that could in principle serve as drugs or industrial enzymes that act more efficiently, effectively and precisely. Artificial proteins could also tell us more about how natural proteins work, by demonstrating how their structure informs their activity and function.
Other applications of the research include conferring virus resistance to specific cells, for use in vaccines or transplants, and manufacturing novel materials endowed with desirable attributes like the ability to withstand high temperatures or pressures.
Revising the Genetic Dictionary
A research team at the Scripps Research Institute in California has now brought us closest to achieving these aims by designing bacterial cells that can replicate, transcribe and translate an artificial DNA base pair. For nearly 20 years, the scientists painstakingly worked out how to add two new custom-made letters to the genome’s natural four-letter vocabulary, integrate them into the cell and synchronize a complex series of processes to make that expanded vocabulary meaningful. The resulting protein made use of an amino acid that the cell wouldn’t normally employ.
The work, published in Nature, represents one of several ongoing efforts to increase the number of amino acids that DNA encodes. Take any organism on earth, and its DNA and RNA have four nucleotide bases, or letters (usually abbreviated as A, T, C and G in DNA; in RNA, another base, U, takes the place of T). Those letters constitute an alphabet that ultimately spells out how to make proteins. But for that to happen, the cell first has to read and translate that alphabet, using a set of rules — the genetic code — to decipher its meaning.
Basically, the cell’s protein-making machinery reads a sequence of DNA as a sentence composed entirely of three-letter words called codons. Codons name amino acids to add sequentially to a protein. With four nucleotide bases at the cell’s disposal, 64 codons are possible: One to six codons specify each of the 20 natural amino acids most commonly used, and three tell the cell to stop building the protein.
By adding a fifth and sixth letter to DNA — which the Scripps researchers, led by Floyd Romesberg, a chemist, have informally labeled as X and Y — the number of available codons explodes to 216.
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