Robust Photocontrol of Elastin-like Polypeptide Phase Transition with a Genetically Encoded Arylazopyrazole

Daniela S. Strugach, Dagan Hadar, Miriam Amiram

Research output: Contribution to journalArticlepeer-review


The rational design of light-responsive proteins and protein-based polymers requires both a photoswitch with suitable light-responsive properties and the ability to incorporate it at (multiple) defined positions in the protein chain. This Letter describes the evolution of high-performance aminoacyl-tRNA synthetases for recognizing a photoswitchable arylazopyrazole-bearing unnatural amino acid (AAP-uAA), which we then incorporated at multiple sites within elastin-like polypeptides (ELPs). The incorporation of AAP-uAA into ELPs yielded proteins capable of an isothermal, reversible, and robust light-mediated soluble-to-insoluble phase transition, which occurred faster (after only 1 min of light irradiation) and demonstrated a larger transition temperature difference (up to a 45 °C difference in the ELP transition temperature upon a cis to trans AAP isomerization) than similar azobenzene-containing ELPs. The evolved translation machinery can be used for the multisite incorporation of AAP at the polypeptide level; moreover, it constitutes a general methodology for designing light-responsive proteins and protein-based polymers with robust light-responsive behavior, made possible by the superior photoswitchable properties of AAP.

Original languageAmerican English
Pages (from-to)2802-2811
Number of pages10
JournalACS Synthetic Biology
Issue number10
StatePublished - 20 Oct 2023


  • arylazopyrazole
  • elastin-like polypeptides
  • genetic code expansion
  • light-responsive proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Biomedical Engineering


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