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Updated: Mar 9, 2026

Author Spotlight: Photo Switchable Protein Recruitment for Reversible Patterning in Artificial Cellular Systems
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Light-directed evolution of dynamic, multi-state, and computational protein functionalities.

Vojislav Gligorovski1, Marco Labagnara1, Lorenzo Scutteri2

  • 1Laboratory of the Physics of Biological Systems, Institute of Physics, EPFL, Lausanne, Switzerland.

Cell
|March 7, 2026
PubMed
Summary
This summary is machine-generated.

Optovolution enables continuous directed evolution of dynamic protein functions by using optogenetics to control protein activity. This method successfully evolved new light-responsive variants and protein logic gates.

Keywords:
El222LOV domainPhyBbudding yeastcell-cycle controldirected evolutiondynamic proteinoptogeneticsprotein logic gatertTAswitchable protein

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Synthetic Biology

Background:

  • Engineering dynamic, multi-state protein functionalities is complex due to the need for selection across all protein states and transitions.
  • Existing methods struggle to apply continuous selection pressure for evolving intricate protein behaviors.

Purpose of the Study:

  • To develop a continuous directed evolution paradigm for proteins with dynamic and multi-state functionalities.
  • To introduce optogenetic control for precise temporal regulation of protein activity during evolution.

Main Methods:

  • Genetically engineered budding yeast with optogenetic inputs to control a protein of interest (POI).
  • The POI's activity was linked to a cell-cycle-essential cyclin, creating dynamic selection pressure.
  • The developed method, termed "optovolution," applies selection pressure on POI cycling at the timescale of minutes.

Main Results:

  • Evolved 19 new variants of the LOV transcription factor El222, including green-light-responsive variants for LOV color-multiplexing.
  • Discovered that YOR1 deletion eliminates the need for phycocyanobilin (PCB) supplementation when evolving the PhyB-Pif3 optogenetic system.
  • Successfully evolved a non-light-responsive AND gate (PEST-rtTA), demonstrating method generality.

Conclusions:

  • Optovolution provides a powerful platform for the continuous evolution of complex protein functionalities.
  • The method facilitates the engineering of dynamic, multi-state, and computational protein behaviors previously challenging to evolve.
  • Optovolution expands the toolkit for protein engineering and synthetic biology applications.