Mapping enzyme activity: From novel diagnostics to target-based therapeutics, how activity-based probes are improving our understanding of biological catalysts

In fond memory of our co-editor Dr. Salomone, whose sudden and untimely passing has left us all deeply saddened and in disbelief. We cherish his invaluable contributions to our Research Topic, which have greatly enriched our collective understanding and left an indelible mark on the depth and quality of our work

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Enzymes are key biological entities that enable living organisms to fulfill a fundamental condition for life: the efficient and selective catalysis of chemical reactions. Unsurprisingly, enzymes offer unique opportunities to improve our understanding of physiological systems, as well as the pathogenesis of challenging human diseases. Every disease process is governed by a particular set of biochemical and molecular mechanisms featuring enzymes, whose activity may lead to the onset of a pathological state. Activity-based probes are highly selective active-site targeted chemicals used to label and monitor the activity state of an enzyme. The clever manipulation of activity-based probes can reveal complex physiological or pathological enzyme-substrate interactions. It can provide critical information on the cellular localization of enzymes, the extent of their expression and function, and foster the annotation of new enzyme drug targets. Cutting-edge technologies now enable functional proteomics and real-time monitoring of enzyme activity down to the cellular level.

More than 20,000 diseases have been reported to affect humans, of which only a relatively small portion are supported by accurate, sensitive and specific diagnostic tests and targeted therapies. The onset of a disease phenotype is governed by the biochemical and molecular shifts from normal physiology that lead to morphological changes, down to the cellular level and the clinical manifestations of disease. This particular aspect of disease is known as pathogenesis, and is often mediated by enzymes. This close association to disease and susceptibility to chemical modulation brings great attractiveness to enzymes as targets for drug discovery. However, uncovering disease biomarkers by high-throughput techniques such as RNAseq, next-generation sequencing and traditional proteomic methodologies often provide global expression profile or protein abundance analysis while overlooking the biochemical amplification caused by enzyme activity. With multilayered posttranslational activity regulation occurring during the onset of disease, significant differences between enzyme abundance and activity are observed, making the precise mapping of enzyme activity across multiple conditions a major unmet need. Functional proteomics, activity-based imaging, and activity-based drug-delivery stand at the forefront of cutting-edge methodologies to address this unmet need, holding great promise in promoting better pharmacological interventions and treatment for critical concerns to human health.

In this Research Topic we navigate through new concepts and technologies that exploit enzyme activity to uncover novel pharmacological approaches in human health. Looking beyond differential gene expression and prevalence of RNA transcripts, we aim to further the goals of proteomics by specifically characterizing enzyme activity instead of protein abundance in the onset of disease states. Furthermore we are beginning to appreciate how the functional activity of enzymes can serve as powerful allies in the early detection and risk-stratification of therapeutically challenging conditions, determine individual response to therapy and enable novel pharmacological approaches in personalized medicine.

We welcome Original Research Articles reporting Basic, Experimental, Translational and Clinical researches addressing, but not limited to, the following topics:
• Global profiling of enzymatic activity in complex samples
• Substrate profiling of disease-relevant enzymes
• Designing active-site targeted chemicals as activity-based probes
• Exploiting enzymatic activity in the design of novel diagnostic tools
• Functional Imaging of disease-relevant enzymes and its pharmacological outcomes
• Profiling enzymatic activity in vivo
• Activity-based probes as tools in advanced pharmacology
• The translational potential of activity based probes in human health

Keywords: Activity-based probes, Enzyme activity, Functional proteomics, Functional Imaging, Enzyme biomarkers

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.