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Cited by 90RNA and protein synthesis mechanismsClick Chemistry and ApplicationsSulfur-Based Synthesis Techniques

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Unleashing the potential of noncanonical amino acid biosynthesis to create cells with precision tyrosine sulfation

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Chen, Yuda, Jin, Shikai, Zhang, Mengxi, Hu, Yu, Wu, Kuan-Lin, Chung, Anna, Wang, Shichao, Tian, Zeru, Wang, Yixian, Wolynes, Peter G., Xiao, Han·2022·Nature Communications
DOI 10.1038/s41467-022-33111-4PMC PMC9481576

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Abstract

Despite the great promise of genetic code expansion technology to modulate structures and functions of proteins, external addition of ncAAs is required in most cases and it often limits the utility of genetic code expansion technology, especially to noncanonical amino acids (ncAAs) with poor membrane internalization. Here, we report the creation of autonomous cells, both prokaryotic and eukaryotic, with the ability to biosynthesize and genetically encode sulfotyrosine (sTyr), an important protein post-translational modification with low membrane permeability. These engineered cells can produce site-specifically sulfated proteins at a higher yield than cells fed exogenously with the highest level of sTyr reported in the literature. We use these autonomous cells to prepare highly potent thrombin inhibitors with site-specific sulfation. By enhancing ncAA incorporation efficiency, this added ability of cells to biosynthesize ncAAs and genetically incorporate them into proteins greatly extends the utility of genetic code expansion methods.

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Metadata

Authors
Chen, Y., Jin, S., Zhang, M., Hu, Y., Wu, K.-L., Chung, A., Wang, S., Tian, Z., Wang, Y., Wolynes, P. G., & Xiao, H.
Affiliations
  • Rice University (US)
  • Center for Theoretical Biological Physics (US)
Corresponding author
Xiao, Han
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2022-09-16
Volume
13
Issue
1
Pages
5434-5434
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-022-33111-4
PMC
PMC9481576
OpenAlex
W4296164994
Cited by
90
References
6
Citations by year
2026: 17 · 2025: 18 · 2024: 26 · 2023: 28 · 2022: 1
FWCI
5.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Rice Research Repository (Rice University) (submittedVersion, cc-by)
Funders
  • Welch Foundation (C-0016, C-1970)
  • National Science Foundation (PHY-2019745)
  • Cancer Prevention and Research Institute of Texas (RR170014)
  • U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R35-GM133706)
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute (R21-CA255894)
  • Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R01-AI165079)
  • U.S. Department of Defense (W81XWH-21-1-0789)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
  • Physical Sciences › Chemistry › Organic Chemistry › Sulfur-Based Synthesis Techniques
Keywords
tyrosine sulfation, sulfotyrosine, genetic code expansion, engineered cells, thrombin inhibitors, membrane permeability, post-translational modification
MeSH terms
Amino Acids, Genetic Code, Proteins, Thrombin, Tyrosine

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