Toward life with a 19–amino acid alphabet through generative artificial intelligence design
. Critically, protein language models and structure-based models were necessary to redesign functional Ile-less proteins in most cases. We systematically replaced all 382 Ile residues from the ribosome and combined 21 redesigned subunits at a native genomic locus to produce a viable, evolutionarily stable cell. This work provides a roadmap to create the first 19-amino acid organism since early evolution.
Authors
- Zetian Zhang (ORCID: https://orcid.org/0009-0009-1392-146X)
- Simon Kozlov (ORCID: https://orcid.org/0009-0009-4689-8745)
- Harris H. Wang (ORCID: https://orcid.org/0000-0003-2164-4318)
- Charlotte Rochereau
- S Ovchinnikov
- X.Y. Liu
- Guillaume Urtecho (ORCID: https://orcid.org/0000-0003-1045-1721)
- Tomasz Blazejewski (ORCID: https://orcid.org/0000-0003-0845-7905)
- Liyuan Liu (ORCID: https://orcid.org/0000-0003-4737-1995)
- Yiming Qu (ORCID: https://orcid.org/0009-0006-5327-8198)
- Jiahui Zhao
- Jasmine Wang
- Avi Swartz
- Yiming Huang
Institutions
- Harvard University (US)
- Harvard University Press (US)
- Massachusetts Institute of Technology (US)
- Columbia University (US)
Publication Details
- Journal
- Science
- Published
- 2026-04-30
- DOI
- https://doi.org/10.1126/science.aeb5171
- Primary Topic
- RNA and protein synthesis mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00