2025-12-01 カリフォルニア大学バークレー校(UCB)
According to the standard genetic code, amino acids are uniquely determined by one or more three-letter codons (top). Some organisms have expanded the code to produce an additional amino acid — in this case, pyrrolysine (bottm). Typically this is done by reinterpreting the UAG stop codon to code for the new amino acid.
<関連情報>
- https://news.berkeley.edu/2025/12/01/all-life-copies-dna-unambiguously-into-proteins-archaea-may-be-the-exception/
- https://www.pnas.org/doi/10.1073/pnas.2517473122
ピロリシンをコードするメタン生成古細菌は曖昧なアンバーコドンの使用を維持している Methanogenic archaea encoding Pyrrolysine maintain ambiguous amber codon usage
Katie E. Shalvarjian, Grayson L. Chadwick, Paloma I. Pérez, +2 , and Dipti D. Nayak
Proceedings of the National Academy of Sciences Published:November 6, 2025
DOI:https://doi.org/10.1073/pnas.2517473122
Significance
Most organisms synthesize proteins using the 20 standard amino acids with a few notable exceptions: those that encode Selenocysteine (Sec) or Pyrrolysine (Pyl). We focus on Pyl, which is widespread in archaea and required for methylamine-mediated methanogenesis. Pyl is encoded by the amber codon (TAG/UAG) and, unlike Sec, mechanisms to conditionally suppress some amber stop codons for Pyl installation during protein synthesis have not been identified. Here, we show that the methanogenic archaeon, Methanosarcina acetivorans, maintains an ambiguous amber codon. We propose that lowering the frequency of amber codons in the genome and balancing Pyl supply with the cellular demand for Pyl allows M. acetivorans to maintain Pyl homeostasis and, in turn, an ambiguous amber codon.
Abstract
Natural genetic code expansion is a phenomenon wherein an additional amino acid is encoded by a stop codon. These nonstandard amino acids are beneficial as they facilitate novel biochemical reactions. However, code expansion leads to ambiguity at the recoded stop codon, which can either be read-through or terminated. Pyrrolysine (Pyl) is encoded by the amber codon (TAG/UAG) and is widespread in archaea, where it is required for methylamine-mediated methanogenesis, an environmentally important metabolism. Mechanisms to conditionally suppress the amber stop codon for Pyl installation during protein synthesis have not been identified. In the model methanogen, Methanosarcina acetivorans, we demonstrate that the UAG codon encodes dual meaning as stop and Pyl. Our data suggest that expression of Pyl biosynthesis and incorporation genes is tuned to the cellular demand for Pyl, which might allow these archaea to navigate ambiguous stop decoding in response to environmental cues.
