Published on: Feb 5, 2025

Engineering A Genomically Recoded Organism With One Stop Codon

Yale researchers recoded E. coli to use one stop codon, freeing two codons to reliably encode two different non-standard amino acids in the same protein.

Protein Engineering

Protein Engineering

Genetic Code / Translation

Genetic Code / Translation

Genome Engineering

Genome Engineering

Synthetic Biology

Synthetic Biology

Researchers engineered a genomically recoded E. coli strain ("Ochre") that uses UAA as the only stop codon by replacing 1,195 UGA (TGA) stops with UAA (TAA) in a ΔTAG background, then tuning release factor 2 and a tryptophan tRNA to reduce native UGA recognition. This compresses stop-codon degeneracy and frees UAG and UGA for reassignment, enabling incorporation of two distinct non-standard amino acids into single proteins with >99% accuracy, advancing toward a fully non-degenerate 64-codon genetic code for synthetic protein design.

DOI: 10.1038/s41586-024-08501-x

Key Takeaways

  • Demonstrates a functional organism with UAA as the sole stop codon (stop-codon compression).

  • Reassigns UAG and UGA for multi-site incorporation of two distinct non-standard amino acids in one protein at >99% accuracy.

  • Advances the roadmap toward a fully non-degenerate 64-codon genetic code, expanding what's manufacturable in synthetic proteins and biotherapeutics.

Institutions

Yale University

New Haven, Connecticut, United States

Yale University - Department of Biomedical Engineering

New Haven, Connecticut, United States

Yale University - Department of Cellular and Molecular Physiology

New Haven, Connecticut, United States

Yale University - Department of Molecular Biophysics and Biochemistry

New Haven, Connecticut, United States

Yale University - Department of Molecular, Cellular and Developmental Biology

New Haven, Connecticut, United States

Yale University - Systems Biology Institute

New Haven, Connecticut, United States

Journal

Springer Nature

Impact Factor: 50.5

Impact Factor: 50.5

Impact Factor: 50.5

Impact Factor: 50.5

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