Unleashing the potential of noncanonical amino acid biosynthesis to create cells with precision tyrosine sulfation
Year: 2022
Type: article
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.
Source: Nature Communications
Institutions: Rice University, Center for Theoretical Biological Physics
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: National Science Foundation, U.S. Department of Defense, U.S. Department of Health and Human Services, Welch Foundation, Cancer Prevention and Research Institute of Texas, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, John S. Dunn Foundation, Rice University, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: Development of Bone-Targeting Antibodies for Ewing Sarcoma Using Genetic Code Expansion, G1267375743, G184053464, G2401486253, G3103861102, G3865632432, G3893316533, G4119534169, G4665238188, G478208587, G4879814465, Recruitment of First-Time, Tenure-Track Faculty Members, ELIMINATING BONE MICROMETASTASES BY BONE-TARGETING ANTIBODIES, G5850682332, Center for Theoretical Biological Physics, G6451644469, G9000215727, G9000292724, Engineering Proteins with Noncanonical Amino Acids, Targeting Siglec-9/Sialoglycan Interactions to Enhance NK Functions During HIV Infection
OpenAlex ID: W4296164994