An Expanded Eukaryotic Genetic Code
Abstract
We describe a general and rapid route for the addition of unnatural amino acids to the genetic code of Saccharomyces cerevisiae . Five amino acids have been incorporated into proteins efficiently and with high fidelity in response to the nonsense codon TAG. The side chains of these amino acids contain a keto group, which can be uniquely modified in vitro and in vivo with a wide range of chemical probes and reagents; a heavy atom–containing amino acid for structural studies; and photocrosslinkers for cellular studies of protein interactions. This methodology not only removes the constraints imposed by the genetic code on our ability to manipulate protein structure and function in yeast, it provides a gateway to the systematic expansion of the genetic codes of multicellular eukaryotes.
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Experiments have demonstrated that the machinery of known life can be manipulated to incorporate many nonbiological amino acids into proteins during translation.
“Experiments have demonstrated that the machinery of known life can be manipulated to incorporate many nonbiological amino acids into proteins during translation (Bain et al., 1989; Noren et al., 1989; Chin et al., 2003).”
From The Astrobiology Primer v2.0 (2016) · cites this paper as Chin et al., 2003
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References 39 · Cited by 820
- Authors
- Chin, J. W., Cropp, T. A., Anderson, J. C., Mukherji, M., Zhang, Z., & Schultz, P. G.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Chin, Jason W.
- Schultz, Peter G.
- ORCID
- Venue
- Science
- Published
- 2003-08-15
- Volume
- 301
- Issue
- 5635
- Pages
- 964-967
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2060391020
- Cited by
- 820
- References
- 39
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 39 · 2023: 34 · 2022: 30 · 2021: 41 · 2020: 32 · 2019: 33 · 2018: 31 · 2017: 36 · 2016: 33 · 2015: 49 · 2014: 61 · 2013: 38 · 2012: 43
- FWCI
- 12.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM62159, R01GM062159)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- genetic code expansion, unnatural amino acids, Saccharomyces cerevisiae, protein modification, protein-protein interaction, protein structure
- MeSH terms
- Superoxide Dismutase-1, Amino Acids, Anticodon, Azides, Escherichia coli, Genetic Code, Humans, Methyltyrosines, Mutation, Phenylalanine, RNA, Transfer, Saccharomyces cerevisiae, Superoxide Dismutase, Protein Biosynthesis, Tyrosine-tRNA Ligase, Codon, Nonsense
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