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Activity-Based Protein Profiling of Non-ribosomal Peptide Synthetases

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Activity-Based Protein Profiling

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 420))

Abstract

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.

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Acknowledgements

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. Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka, 577-8502, Japan

    Fumihiro Ishikawa & Genzoh Tanabe

  2. Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto, 606-8501, Japan

    Hideaki Kakeya

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  3. Hideaki Kakeya
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Corresponding authors

Correspondence to Fumihiro Ishikawa or Hideaki Kakeya .

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Editors and Affiliations

  1. Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA

    Benjamin F. Cravatt

  2. Department of Chemistry, University of Virginia, Charlottesville, VA, USA

    Ku-Lung Hsu

  3. Department of Chemistry, Boston College, Chestnut Hill, MA, USA

    Eranthie Weerapana

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Ishikawa, F., Tanabe, G., Kakeya, H. (2018). Activity-Based Protein Profiling of Non-ribosomal Peptide Synthetases. In: Cravatt, B., Hsu, KL., Weerapana, E. (eds) Activity-Based Protein Profiling. Current Topics in Microbiology and Immunology, vol 420. Springer, Cham. https://doi.org/10.1007/82_2018_133

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