biostudies-literatureBrown WNSFNICHD NIH HHSNIH516-525https://www.ebi.ac.uk/biostudies/studies/S-EPMC10877573biostudies-literatureUnknown19(2)The incorporation of unnatural amino acids into proteins through genetic code expansion has been successfully adapted to African claw-toed frog embryos. Six unique unnatural amino acids are incorporated site-specifically into proteins and demonstrate robust and reliable protein expression. Of these amino acids, several are caged analogues that can be used to establish conditional control over enzymatic activity. Using light or small molecule triggers, we exhibit activation and tunability of protein functions in live embryos. This approach was then applied to optical control over the activity of a RASopathy mutant of NRAS, taking advantage of generating explant cultures from <i>Xenopus</i>. Taken together, genetic code expansion is a robust approach in the <i>Xenopus</i> model to incorporatACS chemical biologyExpanding the Genetic Code of <i>Xenopus laevis</i> Embryos.PMC10877573CHE-1904972R37HD044750R01 HD044750R21 HD106629R21HD106629R37 HD044750Davidson LADeiters ABrown WfalseExpanding the Genetic Code of <i>Xenopus laevis</i> Embryos.The incorporation of unnatural amino acids into proteins through genetic code expansion has been successfully adapted to African claw-toed frog embryos. Six unique unnatural amino acids are incorporated site-specifically into proteins and demonstrate robust and reliable protein expression. Of these amino acids, several are caged analogues that can be used to establish conditional control over enzymatic activity. Using light or small molecule triggers, we exhibit activation and tunability of protein functions in live embryos. This approach was then applied to optical control over the activity of a RASopathy mutant of NRAS, taking advantage of generating explant cultures from <i>Xenopus</i>. Taken together, genetic code expansion is a robust approach in the <i>Xenopus</i> model to incorporat2024-01-01T00:00:00Z2024 Feb2026-05-29T11:40:44.926Z2025-04-19T07:35:13.591ZS-EPMC108775733827777310.1021/acschembio.3c00686