Expanding and Reprogramming the Genetic Code

Dear Colleagues,

The genetic code defines the fundamental rule of translating genetic information into proteins, and is presumably unchanged since its establishment billions of years ago. The 64 base triplets (codons) specify 22 amino acids and translation stops. The additional encoding of new amino acids requires the acquisition of specific molecular machinery and the adjustment of the codon usage in the organism to avoid lethal effects. Due to advanced knowledge and biotechnology, these hurdles have partly been overcome, making substantial progress toward the extensive reprogramming of the genetic code in living cells. The genetic code has successfully been modified, even in animals. Engineered codes could produce proteins, molecular systems/pathways, and organisms never realized in the history of life, through either artificial design or the autonomous evolution of host cells. The currently-available amino acids are almost exclusively confined to tyrosine and pyrrolysine derivatives, and further expansion of the amino-acid repertoire relies on the engineering of new tRNA–aminoacyl-tRNA synthetase pairs. The developed pairs can be used for redefining the meaning of multiple codons simultaneously, after a genome-wide rearrangement in codon usage makes this change viable. Only a few codons are currently useful. On the other hand, expanded codes have found various applications in basic science and industry, and enabled the exploration of biosystems supported by non-natural proteins. This Special Issue will cover original reports and review articles on method developments, applications, and future perspectives of genetic code expansion, as well as natural variations in translational molecules and machinery, which can inspire new directions of engineering.

Dr. Kensaku Sakamoto
Guest Editor

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