The Chemical Biology of Natural Product Biosynthesis: Chemical Tools for the Proteomic Analysis of Nonribosomal Peptide Synthetases

Abstract

Nonribosomal peptides display a broad range of biological activities, including antimicrobial, antitumor and immunosuppressive agents, as well as signaling molecules and virulence factors. Many of these nonribosomal peptides are biosynthesized by large, highly versatile multifunctional proteins known as nonribosomal peptide synthetases (NRPSs). The results of genetic, biochemical, and bioinformatic investigations over the past three decades have offered a profound understanding of the functional characteristics and molecular basis underpinning the enzymology of nonribosomal peptide biosynthesis; however, studies at the proteomic level are limited. This chapter will focus on tools recently developed not only for studies aimed at visualizing, monitoring and tracking NRPS proteins but also for rapid labeling, isolation, identification and enzymatic characterization of NRPS family members as required for proteomics in natural product biosynthesis.

Keywords: Activity-based protein profiling (ABPP), Adenylation domains, Chemical proteomic probes, Chemoproteomics, Competitive ABPP, Nonribosomal peptide synthetases, 5′-O-(N-aminoacyl)-sulfamoyladenosine.

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