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Prodigiosin R3, a new multicyclic prodigiosin formed by prodigiosin cyclization genes in the roseophilin producer

The Journal of Antibiotics volume 76, pages 14–19 (2023)Cite this article

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Abstract

The rph gene cluster for prodigiosin biosynthesis has been identified in Streptomyces griseoviridis 2464-S5, which produces cyclic prodigiosin derivatives including roseophilin (2), prodigiosin R1 (3) and prodigiosin R2 (4). A new cyclic prodigiosin, prodigiosin R3 (1), was produced by the redG redP double disruptant of Streptomyces coelicolor M511 expressing four cyclization gene candidates (rphG, rphG2, rphG3 and rphG4) in the rph cluster. The same compound was isolated from Streptomyces griseoviridis 2464-S5. The molecular formula of 1 was established as C27H33N3O by ESI and FAB mass spectrometry. The structure was determined to be a multicyclic prodigiosin with three alkyl linkages by NMR spectroscopic analysis. Prodigiosin R3 (1) showed cytotoxicity against HeLa human cervical carcinoma cells and HT1080 human fibrosarcoma cells with IC50s of 2.1 µM and 3.2 µM, respectively.

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Acknowledgements

We thank Prof. M. Bibb, John Innes Centre, for providing S. coelicolor M511. We also thank F. Hasegawa, Tokyo University of Science, for assistance with mass spectrometry.

Funding

This work was supported in part by a Grant-in-Aid for Early-Career Scientists 21K14775 (to SK), Japan Society for the Promotion of Science (JSPS).

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Authors and Affiliations

  1. Department of Medicinal and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba, 278-8510, Japan

    Shoko Kimata, Takuya Matsuda & Yoichi Hayakawa

  2. Research Institute for Sustainable Humanosphere, Kyoto University, Uji, Kyoto, 611-0011, Japan

    Takashi Kawasaki

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  1. Shoko Kimata
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  2. Takuya Matsuda
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  4. Yoichi Hayakawa
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Correspondence to Yoichi Hayakawa.

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Kimata, S., Matsuda, T., Kawasaki, T. et al. Prodigiosin R3, a new multicyclic prodigiosin formed by prodigiosin cyclization genes in the roseophilin producer. J Antibiot 76, 14–19 (2023). https://doi.org/10.1038/s41429-022-00572-0

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