Recent advances in proximity labeling: New chemistries, optical control and programmable reaction boundaries

Area of Science:

• Biochemistry
• Chemical Biology
• Molecular Biology

Background:

• Proximity labeling (PL) is a widely used chemical method for mapping molecular interactions within living cells.
• The field is evolving from expanding the PL toolkit to precisely controlling the labeling reaction's boundary.
• Key aspects of control include what is labeled, the timing of labeling, and the propagation distance of reactive intermediates.

Purpose of the Study:

• To review recent advancements in proximity labeling technologies.
• To highlight innovations in genetically encoded systems, optical control, labeling radius refinement, and signal amplification.
• To position proximity labeling as a programmable tool for spatial mapping, molecular recording, and biological intervention.

Main Methods:

• Review of recent literature on proximity labeling techniques.
• Discussion of genetically encoded enzymatic systems replacing traditional chemistries.
• Exploration of optically controlled PL methods, including photoactivated enzymes and photocatalysts.
• Analysis of molecular ruler strategies and engineered enzyme-probe pairs for radius control.
• Examination of emerging platforms for signal integration and functional amplification.

Main Results:

• Development of new genetically encoded enzymatic systems that decrease reliance on peroxide- or biotin-dependent chemistry.
• Advancements in optically controlled PL methods offering improved temporal gating via photoactivated enzymes and related systems.
• Refined control over labeling radius through molecular ruler strategies and engineered enzyme-probe pairs.
• Emergence of novel platforms that repurpose covalent labeling for enhanced signal integration and functional amplification.

Conclusions:

• Recent developments significantly enhance the precision and programmability of proximity labeling.
• These advances expand the utility of PL for detailed spatial mapping of molecular neighborhoods.
• Proximity labeling is poised to become a more versatile tool for molecular recording and targeted biological interventions.