ArticleNature biotechnology2025
Efficient genetic code expansion without host genome modifications.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed.
- Site-Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids.Angewandte Chemie (International ed. in English) · 2026Review
- Structural adaptations for enhanced translation kinetics in evolved ribosomes.Nucleic acids research · 2026Article
- Engineering Protease-Resistant Peptides via Non-Canonical Amino Acids: Design Strategies and Biosynthetic Advances.Bioengineering (Basel, Switzerland) · 2026Review
- Genetic Incorporation of Diverse Noncanonical Amino Acids for Histidine Substitution.Journal of the American Chemical Society · 2026Article
- Recoding multiple rare codons enables the simultaneous incorporation of up to five distinct noncanonical amino acids.Nature chemistry · 2026Article
- Methods for studying the effects of phosphorylation patterns in proteins.Biochemical Society transactions · 2026Review
- Structural adaptations for enhanced translation kinetics in evolved ribosomes.bioRxiv : the preprint server for biology · 2026Article
- Chemical biology approaches to study and target circadian clocks and their components.FEBS letters · 2026Review
- ENSURE: the encyclopedia of suppressor tRNA with an AI assistant.Nucleic acids research · 2026Article
- Engineered orthogonal translation systems from metagenomic libraries expand the genetic code.bioRxiv : the preprint server for biology · 2025Article
- A robust platform streamlining aromatic noncanonical amino acid biosynthesis and genetic code expansion in Escherichia coli.Nature communications · 2025Article
- Strategies to Expand the Genetic Code of Mammalian Cells.Chemical reviews · 2025Review
- Long-Range Electrostatics in Serine Proteases: Machine Learning-Driven Reaction Sampling Yields Insights for Enzyme Design.Journal of chemical information and modeling · 2025Article
- Hierarchical metabolic engineering for rewiring cellular metabolism.FEMS microbiology reviews · 2025Review
- Toward a Quadruplet Codon Mitochondrial Genetic Code.ACS synthetic biology · 2024Article
- Engineering a controllable and reversible switch for CAR-based cellular immunotherapies via a genetic code expansion system.Journal of hematology & oncology · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors.
Funding
Abstract
Supplementing translation with noncanonical amino acids (ncAAs) can yield protein sequences with new-to-nature functions but existing ncAA incorporation strategies suffer from low efficiency and context dependence. We uncover codon usage as a previously unrecognized contributor to efficient genetic code expansion using non-native codons. Relying only on conventional Escherichia coli strains with native ribosomes, we develop a plasmid-based codon compression strategy that minimizes context dependence and improves ncAA incorporation at quadruplet codons. We confirm that this strategy is compatible with all known genetic code expansion resources, which allowed us to identify 12 mutually orthogonal transfer RNA (tRNA)-synthetase pairs. Enabled by these findings, we evolved and optimized five tRNA-synthetase pairs to incorporate a broad repertoire of ncAAs at orthogonal quadruplet codons. Lastly, we extend these resources to an in vivo biosynthesis platform that can readily create >100 new-to-nature peptide macrocycles bearing up to three unique ncAAs. Our approach will accelerate innovations in multiplexed genetic code expansion and the discovery of chemically diverse biomolecules.
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39261591What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.