Natural products and their biological targets: proteomic and metabolomic labeling strategies

Abstract

Activity-based protein profiling (ABPP) has matured into a standard method for the fast, sensitive, and selective identification of enzyme activity and inhibitors in proteomes. By using natural product based probes, the targets of many uncharacterized molecules can be easily identified in complex proteomes, and their exact function and mechanism of action understood. Natural products and their derivatives can also serve as pharmaceutical lead structures that impede essential components in the cell and their effects can be studied in biological assays. Since the complex regulatory processes in a cell go beyond mere transcription, translation, and activation, it is imperative to also identify the products of the active proteome--the metabolites and binding partners of individual enzymes and proteins. Therefore, methods by which the chemically complex metabolome can be characterized are necessary. A series of interesting approaches have become available in recent years that enable the global investigation of enzyme-metabolite pairs.