Modulating Protein Function through Genetically Encoded Oxidative Chemistry
Hengyu Li1, Alen Pavlič1, Noor E Ibrahim1
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
Journal of the American Chemical Society
|June 3, 2026
Summary
Researchers developed genetically encoded oxidative chemistry to control protein function in cells. This programmable system uses light-activated miniSOG to generate reactive oxygen species (ROS), enabling tunable modulation of protein activity and localization.
Area of Science:
- Cell Biology
- Biochemistry
- Biotechnology
Background:
- Oxidative chemistry plays a role in cellular signaling but is not widely used for programmable protein regulation.
- Existing methods for controlling protein function in cells have limitations in programmability and spatial organization.
Purpose of the Study:
- To establish genetically encoded oxidative chemistry as a tunable framework for modulating protein function in living cells.
- To demonstrate the spatial and temporal control of protein activity using light-activated reactive oxygen species (ROS).
Main Methods:
- Utilized miniSOG, a genetically encoded photosensitizer, to generate ROS upon illumination.
- Coupled miniSOG to specific intracellular contexts and proteins of interest, including redox reporters and ion channels.
- Employed pathway-selective scavengers to investigate the selectivity of oxidative perturbation.
Main Results:
- Demonstrated that controlled intracellular oxidation activates redox-sensitive TRP ion channels (TRPA1, TRPV1) and increases fluorescence of HyPerRed.
- Showed that modulation strength and kinetics are tunable via illumination parameters, expression ratios, and subcellular localization.
- Confirmed context-specific targeting of soluble and membrane proteins, with enhanced coupling to membrane effectors via membrane targeting.
Conclusions:
- Genetically encoded oxidative chemistry provides a versatile and spatially organized modality for engineering protein function.
- This approach allows for precise, light-inducible control over protein activity within a defined cellular operating regime.
- The framework is extendable to protein-proximal and native cellular settings, including modulation of endogenous proteins.
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