Abstract

A repertoire of proteolysis-targeting signals known as degrons is a necessary component of protein homeostasis in every living cell. In bacteria, degrons can be used in place of chemical genetics approaches to interrogate and control protein function. Here, we provide a comprehensive review of synthetic applications of degrons in targeted proteolysis in bacteria. We describe recent advances ranging from large screens employing tunable degradation systems and orthogonal degrons, to sophisticated tools and sensors for imaging. Based on the success of proteolysis-targeting chimeras as an emerging paradigm in cancer drug discovery, we discuss perspectives on using bacterial degraders for studying protein function and as novel antimicrobials.

Highlights

  • Proteins in living cells undergo a constant process of synthesis and degradation

  • This review focuses on the existing applications of bacterial degradation signals in the context of introducing Targeted Protein Degradation (TPD) in bacteria as an approach to proteome engineering and developing novel degron-based antimicrobials

  • C. crescentus SspB and the degron optimized for this adaptor were used in parallel to E. coli degradation components to show that the system can be modified for more complex applications enabling orthogonal regulation of degradation of two proteins simultaneously (Griffith and Grossman, 2008)

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Summary

Introduction

Proteins in living cells undergo a constant process of synthesis and degradation. Protein degradation helps to maintain protein homeostasis by eliminating toxic aberrant proteins or regulating the levels of proteins needed under the given environmental conditions. Protein degradation in bacteria is performed by proteases such as Clp complexes, Lon or the bacterial 20S proteasome which contain AAA+ domains (Table 1; Sauer and Baker, 2011).

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