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Published on: October 14, 2025
Proteases in bacteriophage defense systems and their potential in bioengineering
Konstantinos Kalogeropoulos1, Sam P B van Beljouw2, Dani Feldmann2
1Department of Bionanoscience, Delft University of Technology, 2629 HZ Delft, The Netherlands; Kavli Institute of Nanoscience, 2629 HZ Delft, The Netherlands; Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads B221, Kgs. Lyngby, 2800, Denmark.
None:
Novel phage defense systems featuring diverse enzymatic activities are continually being discovered. Among these, defense systems employing proteolytic enzymes have been identified, revealing a previously unrecognized enzymatic activity in phage defense. These protease-associated defense systems represent an untapped reservoir for new biotechnological tools and may serve as a springboard for the development of proteome editors. This review outlines recent advancements in the discovery and characterization of protease-containing defense systems, proposes methods for further exploration and investigation of protease activity, and considers the prospect of protease defense systems for modulating protein processing and cell fate.
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