Modulating Protein Function through Genetically Encoded Oxidative Chemistry

Oxidative chemistry underlies many endogenous signaling pathways but remains underutilized as a programmable strategy for regulating protein function in living cells. Here we establish genetically encoded oxidative chemistry as a tunable framework for modulating diverse proteins by coupling a photosensitizer to defined intracellular contexts. Using miniSOG to generate reactive oxygen species (ROS), we show that controlled intracellular oxidation increases the fluorescence of the redox reporter HyPerRed and activates redox-sensitive TRP ion channels, with strong responses in TRPA1 and TRPV1 but not TRPV4. Pathway-selective scavengers reveal differential coupling of soluble and membrane target