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Thiofrenomycins, new kalafungin-type pyranonaphthoquinone skeleton with sulfide linkage from Streptomyces sp. MM863L-181F9

The Journal of Antibiotics volume 79, pages 67–73 (2026)Cite this article

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Abstract

Neisseria gonorrhoeae is the bacterium that causes gonorrhea, and multidrug resistance is becoming progressively more severe in many countries. Therefore, limited drugs are available for treatment. It is predicted that further drug resistance will be acquired, making treatment still more difficult, so there is an urgent need to develop new drugs. We discovered three compounds with a new kalafungin-type pyranonaphthoquinone skeleton, thiofrenomycins A-C, that exhibit strong antibacterial activity against N. gonorrhoeae in a culture solution of Streptomyces sp. MM863L-181F9 derived from fallen leaves. The absolute stereochemistry of these compounds was determined using X-ray crystal structure analysis. These substances exhibit minimal inhibitory concentrations of 0.125–16 µg/mL against N. gonorrhoeae.

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Acknowledgements

We thank Y. Kubota, Y. Takahashi and K. Iijima for technical assistance in determining the structure of thiofrenomycins. We also thank Y. Shibuya for technical support for the genetic modification of N. gonorrhoeae strains and R. Onodera for cytotoxicity assay. We gratefully acknowledge the contributions of the researchers and institutions who provided bacterial strains for this study. Their support was crucial for the success of this research. We thank Laura Murray, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Institute of Microbial Chemistry (BIKAKEN) 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo, Japan

    Tomoyuki Kimura, Yoshimasa Ishizaki, Maya Umekita, Rie Arisaka, Hideyuki Muramatsu, Chigusa Hayashi, Ryuichi Sawa & Masayuki Igarashi

  2. Institute of Microbial Chemistry (BIKAKEN), Numazu, 18-24 Miyamoto, Numazu-shi, Shizuoka, Japan

    Isao Momose

  3. Department of Latent Infection, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan

    Ken Shimuta

  4. Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan

    Ken Shimuta

  5. Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan

    Ken Shimuta

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  1. Tomoyuki Kimura
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  2. Yoshimasa Ishizaki
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Correspondence to Ryuichi Sawa or Masayuki Igarashi.

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Kimura, T., Ishizaki, Y., Umekita, M. et al. Thiofrenomycins, new kalafungin-type pyranonaphthoquinone skeleton with sulfide linkage from Streptomyces sp. MM863L-181F9. J Antibiot 79, 67–73 (2026). https://doi.org/10.1038/s41429-025-00883-y

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