PUBLICATION

Chemically Acylated tRNAs are Functional in Zebrafish Embryos

Authors
Brown, W., Galpin, J.D., Rosenblum, C., Tsang, M., Ahern, C.A., Deiters, A.
ID
ZDB-PUB-230122-2
Date
2023
Source
Journal of the American Chemical Society   145(4): 2414-2420 (Journal)
Registered Authors
Tsang, Michael
Keywords
none
MeSH Terms
  • Amino Acids/chemistry
  • Amino Acyl-tRNA Synthetases*/genetics
  • Amino Acyl-tRNA Synthetases*/metabolism
  • Animals
  • Genetic Code
  • Histidine/genetics
  • RNA, Transfer*/genetics
  • RNA, Transfer*/metabolism
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
PubMed
36669466 Full text @ J. Am. Chem. Soc.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping