Scientists supported in part by the NASA Astrobiology Program have described how a semi-synthetic organism is able to use DNA that contains nucleotides not used in nature to produce proteins that include noncanonical amino acids (ncAAs). Life on Earth uses DNA with a four-letter genetic alphabet composed of the nucleotides adenine, guanine, cytosine, and thymine. In a strand of DNA, these nucleotides are organized in groups of three, known as a triplet codons. These codons tell a cell which amino acids to use when building specific proteins. For life on Earth, this system is composed of 64 triplet codons that encode proteins constructed from 20 amino acids.

Previously, the team was able to incorporate ‘unnatural’ nucleotides into strands of DNA, allowing for the formation of semi-synthetic organisms that have additional codons beyond the 64 natural ones. The new study provides a systematic analysis of these unnatural codons. The scientists identified nine codons that are able to produce unnatural proteins that incorporate amino acids beyond the canonical twenty. Three of these nine codons can be decoded by the semi-synthetic organism, which means that the team has identified the first 67-codon organism. The researchers believe that being able to incorporate ncAAs into a protein could allow for the development of proteins with unique traits, as well as semi-synthetic organisms with new forms and functions.

The study, “New codons for efficient production of unnatural proteins in a semisynthetic organism,” was published in the journal Nature: Chemical Biology. The work was supported by NASA Astrobiology through the Exobiology Program. This newly-revealed science is also a critical part of NASA’s work to understand the Universe, advance human exploration, and inspire the next generation. As NASA’s Artemis program moves forward with human exploration of the Moon, the search for life on other worlds remains a top priority for the agency.

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