Intein Zymogens: Conditional Assembly and Splicing of Split Inteins via Targeted Proteolysis

J Am Chem Soc. 2017 Jun 21;139(24):8074-8077. doi: 10.1021/jacs.7b02618. Epub 2017 Jun 7.


Naturally split inteins have found widespread use in chemical biology due to their ability to drive the ligation of separately expressed polypeptides through a process termed protein trans-splicing (PTS). In this study, we harness PTS by rendering association of split intein fragments conditional upon the presence of a user-defined protease. We show that these intein "zymogens" can be used to create protein sensors and actuators that respond to the presence of various stimuli, including bacterial pathogens, viral infections, and light. We also show that this design strategy is compatible with several orthogonal split intein pairs, thereby opening the way to the creation of multiplexed sensor systems.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Enzyme Precursors / chemistry*
  • Enzyme Precursors / metabolism*
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Inteins*
  • Peptides / chemistry*
  • Peptides / metabolism*
  • Protein Splicing*
  • Proteolysis*


  • Enzyme Precursors
  • Peptides
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins