Chemically Acylated tRNAs are Functional in Zebrafish Embryos

Wes Brown; Jason D Galpin; Carolyn Rosenblum; Michael Tsang; Christopher A Ahern; Alexander Deiters

doi:10.1021/jacs.2c11452

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Chemically Acylated tRNAs are Functional in Zebrafish Embryos

Journal article

Open access

Peer reviewed

Chemically Acylated tRNAs are Functional in Zebrafish Embryos

Wes Brown, Jason D Galpin, Carolyn Rosenblum, Michael Tsang, Christopher A Ahern and Alexander Deiters

Journal of the American Chemical Society, Vol.145(4), pp.2414-2420

02/01/2023

DOI: 10.1021/jacs.2c11452

PMCID: PMC10155198

PMID: 36669466

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https://pmc.ncbi.nlm.nih.gov/articles/PMC10155198/pdf/nihms-1891545.pdfView

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Abstract

Genetic code expansion has pushed protein chemistry past the canonical 22 amino acids. The key enzymes that make this possible are engineered aminoacyl tRNA synthetases. However, as the number of genetically encoded amino acids has increased over the years, obvious limits in the type and size of novel side chains that can be accommodated by the synthetase enzyme become apparent. Here, we show that chemically acylating tRNAs allow for robust, site-specific incorporation of unnatural amino acids into proteins in zebrafish embryos, an important model organism for human health and development. We apply this approach to incorporate a unique photocaged histidine analogue for which synthetase engineering efforts have failed. Additionally, we demonstrate optical control over different enzymes in live embryos by installing photocaged histidine into their active sites.

Details

Title: Subtitle: Chemically Acylated tRNAs are Functional in Zebrafish Embryos
Creators: Wes Brown - University of Pittsburgh
Jason D Galpin - University of Iowa
Carolyn Rosenblum - University of Pittsburgh
Michael Tsang - University of Pittsburgh
Christopher A Ahern - University of Iowa
Alexander Deiters - University of Pittsburgh
Resource Type: Journal article
Publication Details: Journal of the American Chemical Society, Vol.145(4), pp.2414-2420
DOI: 10.1021/jacs.2c11452
PMID: 36669466
PMCID: PMC10155198
NLM abbreviation: J Am Chem Soc
ISSN: 0002-7863
eISSN: 1520-5126
Grant note: DOI: 10.13039/100007921, name: University of Pittsburgh; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01GM132565, R24NS104617
Language: English
Electronic publication date: 01/20/2023
Date published: 02/01/2023
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984361749202771

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