Deciphering the physiological role of serine enzymes involved in mycobacterial lipid metabolism using activity-based protein profiling

The importance of lipids as key players in the physiology, life cycle, and virulence of mycobacterial-related diseases, such as tuberculosis caused by the pathogenic bacteria M. tuberculosis, has been well established. These lipids participate in the host–pathogen cross-talk and play crucial roles in key cellular processes, including bacterial growth, virulence (reactivation and propagation), dormancy, cell wall biosynthesis, as well as in lipid storage and degradation. In this context, activity-based protein profiling has emerged as a powerful chemoproteomic strategy to identify and characterize the mycobacterial enzymes responsible for the synthesis and degradation of these lipids. Herein, we highlight the use of serine enzyme inhibitors as activity-based probes for the identification and characterization of the functional state of mycobacterial serine enzymes within the bacteria.