Serene? So last century. Valine? On it. Glycine? You have got to be kidding me.
Those chemicals are part of the 20 amino acids that are usually incorporated into proteins. That means they have a unique place in the so-called genetic code, which translates between DNA bases into the amino acids of proteins.
Indeed, the genetic code has enabled all the diversity and complexity of life on Earth, from E. Koli to T. rex. But still, researchers are beginning to find this kind of limitation. Life has found ways of using more than 140 amino acids in proteins; and once we start tinkering with things, we can do scads more. Just because evolution has done so does not mean we need to trust only 20 old boring ones. What follows is a look at how and why we want to engineer synthetic amino acids into living cells and organisms.
Meaning of Tweaking
Transfer RNAs (tRNAs) act as a bridge between DNA and amino acids—the DNA-based instructions for how to make protein and the protein itself. Each set of three bases in DNA can make up one of the 20 canonical amino acids. The tRNAs “read” this gene triplet and insert the selected amino acid into the growing protein. So in order to add a new amino acid to proteins, researchers have had to engineer—or in rare cases, find in microbes—a tRNA molecule that will insert into proteins when presented with a specific DNA code.
In most cases, the DNA triplet used is not one that already specifies an amino acid. Instead, it is one that signals the cell to stop adding amino acids to a protein. Most organisms have three of these stop codes and, with a bit of technology, can get by with two. Scientists can then insert this stop sequence into the middle of genes with a tRNA that responds to it. When a gene is translated into a protein, the tRNA adds an artificial amino acid into the elongating protein chain. Therefore, scientists must provide the cell with an artificial amino acid as well.
Using this technique, synthetic amino acids have been incorporated into plants and laboratory animals including roundworms, fruit flies, and mice. Mostly, it is used to study the viruses themselves.
First, the technique is used to label specific proteins to understand where and when the protein is made. Other uses include eating proteins that are attached to any proteins they interact with until the (chemical) researchers tell them to let it go. This allows researchers to find protein bonds that might otherwise be too short to see. It is also possible to use artificial amino acids to block protein activity, again in a way that can be raised at will. This ability to turn protein activity on and off in a selected cell type and at a selected time may help elucidate protein function and may also be used in therapy.
It is also possible to track how cells manage their viruses. Many proteins are activated, deactivated, or targeted for destruction by adding small chemicals to them (things like phosphates, acetyl groups, or others). The synthetic amino acid method allows researchers to slip in amino acids that are pre-modified in some way. Controlling when and where these changes occur can allow us to better understand what happens to the protein after it has been changed.
On the other hand, you can try something completely different. Other researchers are adding in amino acids “with new chemical structures and properties that have allowed the evolution of proteins with novel or enhanced function.”
To the hospital?
This work has remained in the area of basic research, but hospitals and even commercial opportunities abound. Changing antibiotics or other immunosuppressive agents may allow doctors to turn on and off their work at better times and places. An artificial amino acid can be inserted into the target protein to enhance the specificity and thus the effect of the targeted drug.
Creating pathogens that rely on artificial amino acids could provide a new way of making fewer bugs for vaccines—after all, they can’t reproduce in cells that lack the necessary artificial tRNAs.
Since all tRNAs add subunits to growing chains, some think they may one day be harnessed to go beyond connecting amino acids to make proteins. Depending on the building blocks they are given, they can be used to make all kinds of polymers.
Another way to get artificial amino acids into proteins is to change the genetic code read by tRNA molecules. Since there are four different bases used by genes (A, T, C, and G), there are currently 64 bases to code for the 20 canonical amino acids. These 64 are all that the researcher can mess with. But they’ve made tRNAs that can recognize groups of four nucleotides instead of three, giving them 256 different combinations. That means 256 possible synthetic amino acids—or whatever molecular protein scientists call it is expected next—for scientists to play with.
Given that most amino acids can occur naturally, everyone thinks that life ended up basically on your list of 20 even by accident. With our ability to modify genes, we are poised to greatly expand the list of what life can do with.
Creation2017. DOI: 10.1038/nature24031 (About DOIs).