Expanding The Genetic Code Via Mutant Aminoacyl TRNA Synthetases
In some of the aminoacyl tRNA synthetases, the cavity that holds the amino acid can be mutated and modified to carry artificial, unnatural amino acids synthesized in the lab, and to attach them to specific tRNAs. This expands the genetic code, beyond the twenty amino acids universal in nature, to include an unnatural amino acid as well. The unnatural amino acid is coded by an otherwise non-coding base triplet such as the amber stop codon. The organism that expresses the mutant synthetase can then be genetically programmed to incorporate the unnatural amino acid into any desired position in any protein of interest, allowing biochemists or structural biologists to probe or change the protein's function. For instance, one can start with the gene for a protein that binds a certain sequence of DNA, and, by directing an unnatural amino acid with a reactive side-chain into the binding site, create a new protein that cuts the DNA at the target-sequence, rather than binding it.
By mutating aminoacyl tRNA synthetases, chemists have expanded the genetic codes of various organisms to include lab-synthesized amino acids with all kinds of useful properties: photoreactive, metal-chelating, xenon-chelating, crosslinking, color-changing, spin-resonant, fluorescent, biotinylated, and redox-active amino acids.
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