Activity-Based Protein Profiling of Non-ribosomal Peptide Synthetases

  • Fumihiro IshikawaEmail author
  • Genzoh Tanabe
  • Hideaki KakeyaEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 420)


Non-ribosomal peptide (NRP) natural products are one of the most promising resources for drug discovery and development because of their wide-ranging of therapeutic potential, and their behavior as virulence factors and signaling molecules. The NRPs are biosynthesized independently of the ribosome by enzyme assembly lines known as the non-ribosomal peptide synthetase (NRPS) machinery. Genetic, biochemical, and bioinformatics analyses have provided a detailed understanding of the mechanism of NRPS catalysis. However, proteomic techniques for natural product biosynthesis remain a developing field. New strategies are needed to investigate the proteomes of diverse producer organisms and directly analyze the endogenous NRPS machinery. Advanced platforms should verify protein expression, protein folding, and activities and also enable the profiling of the NRPS machinery in biological samples from wild-type, heterologous, and engineered bacterial systems. Here, we focus on activity-based protein profiling strategies that have been recently developed for studies aimed at visualizing and monitoring the NRPS machinery and also for rapid labeling, identification, and biochemical analysis of NRPS enzyme family members as required for proteomic chemistry in natural product sciences.


Natural product biosynthesis Non-ribosomal peptide synthetase Adenylation domain Thiolation domain Activity-based probe 



This work was supported by the Japan Society for the Promotion of Science (JSPS) through a Grant-in Aid for Scientific Research on Innovative Areas [17H05438 (F.I.) and 17H06401 (H.K.)] and the Antiaging Project for Private Universities.

Conflict of Interest

The authors declare no competing financial interest.


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Authors and Affiliations

  1. 1.Faculty of PharmacyKindai UniversityHigashi-Osaka, OsakaJapan
  2. 2.Graduate School of Pharmaceutical SciencesKyoto UniversitySakyo, KyotoJapan

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