Scientists Developing Custom DNA That Expands Letters from 4 to 6, and Beyond

It’s time, time to go beyond nature.  Right?  The fundamental building blocks of nature are found in the DNA code.  But what if human beings could create a DNA code base that goes beyond what nature currently allows?  That’s what a team in California is working on.  What could go wrong?

From Quanta Magazine

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 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…..

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.

The Scripps team’s accomplishment does not stand alone. Steven Benner, a chemist at the Foundation for Applied Molecular Evolution in Florida, and his colleagues have made a 12-letter genetic alphabet(although they have not put their new base pairs into a living cell). In both cases, having more bases offers lots of latitude to bring nonstandard amino acids into proteins with never-before-seen forms and functions.

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