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Comprehensive analysis of biosynthetic gene clusters in bacteria and discovery of Tumebacillus as a potential producer of natural products

The Journal of Antibiotics volume 76, pages 316–323 (2023)Cite this article

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Abstract

Limited microbial genera such as Streptomyces have served as sources of natural products (NPs), whereas most others have been less investigated. The vast accumulation of genomic data available in the NCBI database enables us to bioinformatically estimate the ability of other microbial groups to produce NPs. We analyzed 21,052 complete bacterial genome sequences using antiSMASH and compared the average numbers of biosynthetic gene clusters (BGCs) related to polyketides, non-ribosomal peptides, and/or terpenes biosynthesis at the genus level. Our bioinformatic analyses showed that Tumebacillus has 5–15 BGCs and is a promising NP producer. We searched for NPs from the culture broth of Tumebacillus permanentifrigoris JCM 14557T and found two novel compounds (tumebacin with anti-Bacillus activity and tumepyrazine) and identified two known compounds. Our results highlight the diversity of sources of NPs awaiting discovery.

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Acknowledgements

We are grateful to Distinguished Emeritus Professor Satoshi Ōmura (Kitasato University) for his helpful support and valuable guidance and suggestions. We are grateful to Dr. Kenichiro Nagai and Ms. Noriko Sato (School of Pharmacy, Kitasato University) for the mass and NMR spectral measurements. This study was partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research; BINDS) of the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP19am0101096 and JP22ama121035.

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Authors and Affiliations

  1. Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Yuta Kikuchi, Masato Iwatsuki, Aoi Kimishima, Hayama Tsutsumi, Yukihiro Asami & Yuki Inahashi

  2. Graduate School of Science, Kitasato University, 1-15-1, Kitazato, Minami, Sagamihara, Kanagawa, 252-0373, Japan

    Miku Kawashima

  3. Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Masato Iwatsuki, Aoi Kimishima, Hayama Tsutsumi, Yukihiro Asami & Yuki Inahashi

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  1. Yuta Kikuchi
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Correspondence to Yuki Inahashi.

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Kikuchi, Y., Kawashima, M., Iwatsuki, M. et al. Comprehensive analysis of biosynthetic gene clusters in bacteria and discovery of Tumebacillus as a potential producer of natural products. J Antibiot 76, 316–323 (2023). https://doi.org/10.1038/s41429-023-00609-y

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