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New polycyclic tetramate macrolactams with antimycobacterial activity produced by marine-derived Streptomyces sp. KKMA-0239

The Journal of Antibiotics volume 77, pages 265–271 (2024)Cite this article

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Abstract

During our screening for anti-mycobacterial agents against Mycobacterium avium complex (MAC), two new polycyclic tetramate macrolactams (PTMs), named hydroxycapsimycin (1) and brokamycin (2), were isolated along with the known PTM, ikarugamycin (3), from the culture broth of marine-derived Streptomyces sp. KKMA-0239. The relative structures of 1 and 2 were elucidated by spectroscopic data analyses, including 1D and 2D NMR. Furthermore, the absolute configuration of 1 was confirmed by a single-crystal X-ray diffraction analysis. Compounds 2 and 3 exhibited moderate antimycobacterial activities against MAC, including clinically isolated drug-resistant M. avium.

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References

  1. Adjemian J, Olivier KN, Seitz AE, Holland SM, Prevots DR. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries. Am J Respir Crit Care Med. 2012;185:881–6.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Namkoong H, Kurashima A, Morimoto K, Hoshino Y, Hasegawa N, Ato M, et al. Epidemiology of pulmonary nontuberculous mycobacterial disease, Japan. Emerg Infect Dis. 2016;22:1116–7.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Fernandez-Pittol M, Batista-Arnau S, Román A, San Nicolás L, Oliver L, González-Moreno O, et al. Differences in drug-susceptibility patterns between mycobacterium avium, mycobacterium intracellulare, and mycobacterium chimaera clinical isolates: prospective 8.5-year analysis by three laboratories. Antibiotics. 2022;12:64.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hosoda K, Koyama N, Kanamoto A, Tomoda H. Discovery of nosiheptide, griseoviridin, and etamycin as potent anti-mycobacterial agents against mycobacterium avium complex. Molecules. 2019;24:1495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Koyama N, Shigeno S, Kanamoto A, Tomoda H. Steffimycin E, a new anti-mycobacterial agent against Mycobacterium avium complex, produced by Streptomyces sp. OPMA02852. J Antibiot. 2020;73:581–4.

    Article  CAS  Google Scholar 

  6. Hikima A, Asamizu S, Onaka H, Zhang H, Tomoda H, Koyama N. Kimidinomycin, a new antibiotic against Mycobacterium avium complex, produced by Streptomyces sp. KKTA-0263. J Antibiot. 2022;75:72–6.

    Article  CAS  Google Scholar 

  7. Koyama N, Kojima S, Nonaka K, Masuma R, Matsumoto M, Omura S, et al. Calpinactam, a new anti-mycobacterial agent, produced by Mortierella alpina FKI-4905. J Antibiot. 2010;63:183–6.

    Article  CAS  Google Scholar 

  8. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard—Ninth Edition, vol. 32, 9ed. Wayne, PA, USA, 2012.

  9. Yan X, Li Y, Wang N, Chen Y, Huang LL. Streptomyces ginkgonis sp. nov., an endophyte from Ginkgo biloba. Antonie Van Leeuwenhoek. 2018;111:891–6.

    Article  CAS  PubMed  Google Scholar 

  10. Liu C, Wang X, Zhao J, Liu Q, Wang L, Guan X, et al. Streptomyces harbinensis sp. nov., an endophytic, ikarugamycin-producing actinomycete isolated from soybean root [Glycine max (L.) Merr]. Int J Syst Evol Microbiol. 2013;63:3579–84.

    Article  CAS  PubMed  Google Scholar 

  11. Yokoi K, Hasegawa H, Sato J, Matsumoto M. New antibiotic SS8201D and its manufacturing method: S. S. Pharmaceutical Co., Ltd.; 1984.

  12. Lacret R, Oves-Costales D, Gómez C, Díaz C, de la Cruz M, Pérez-Victoria I, et al. New ikarugamycin derivatives with antifungal and antibacterial properties from Streptomyces zhaozhouensis. Mar Drugs. 2014;13:128–40.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Jomon K, Kuroda Y, Ajisaka M, Sakai H. A new antibiotic, ikarugamycin. J Antibiot. 1972;25:271–80.

    Article  CAS  Google Scholar 

  14. Jiang M, Chen S, Li J, Liu L. The biological and chemical diversity of tetramic acid compounds from marine-derived microorganisms. Mar Drugs. 2020;18:114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhang W, Zhang G, Zhang L, Liu W, Jiang X, Jin H, et al. New polycyclic tetramate macrolactams from marine-derived Streptomyces sp. SCSIO 40060. Tetrahedron. 2018;74:6839–45.

    Article  CAS  Google Scholar 

  16. Antosch J, Schaefers F, Gulder TA. Heterologous reconstitution of ikarugamycin biosynthesis in E. coli. Angew Chem Int Ed Engl. 2014;53:3011–4.

    Article  CAS  PubMed  Google Scholar 

  17. Li Y, Chen H, Ding Y, Xie Y, Wang H, Cerny RL, et al. Iterative assembly of two separate polyketide chains by the same single-module bacterial polyketide synthase in the biosynthesis of HSAF. Angew Chem Int Ed Engl. 2014;53:7524–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhang G, Zhang W, Zhang Q, Shi T, Ma L, Zhu Y, et al. Mechanistic insights into polycycle formation by reductive cyclization in ikarugamycin biosynthesis. Angew Chem Int Ed Engl. 2014;53:4840–4.

    Article  CAS  PubMed  Google Scholar 

  19. Yu HL, Jiang SH, Bu XL, Wang JH, Weng JY, Yang XM, et al. Structural diversity of anti-pancreatic cancer capsimycins identified in mangrove-derived Streptomyces xiamenensis 318 and post-modification via a novel cytochrome P450 monooxygenase. Sci Rep. 2017;7:40689.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Blodgett JA, Oh DC, Cao S, Currie CR, Kolter R, Clardy J. Common biosynthetic origins for polycyclic tetramate macrolactams from phylogenetically diverse bacteria. Proc Natl Acad Sci USA. 2010;107:11692–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fukuda T, Takahashi M, Kasai H, Nagai K, Tomoda H. Chlokamycin, a new chloride from the marine-derived streptomyces sp. MA2-12. Nat Prod Commun. 2017;12:1934578X1701200818.

    CAS  Google Scholar 

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Acknowledgements

We express our thanks to Ms. Noriko Sato and Ms. Reiko Seki, the School of Pharmacy, Kitasato University for instrumental measurements and Mr. Shunto Kubota, the School of Pharmacy, Kitasato University for assisting with our experiments. This work was supported by the Uehara Memorial Foundation (to HT) and a Kitasato University Research Grant for Young Researchers (to SS).

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Authors and Affiliations

  1. Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Satoru Shigeno, Miyu Kadowaki, Kanji Hosoda, Hiroshi Tomoda & Taichi Ohshiro

  2. Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Satoru Shigeno, Miyu Kadowaki, Kenichiro Nagai, Kanji Hosoda, Hiroshi Tomoda & Taichi Ohshiro

  3. Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, 4-5-7 Konan, Minato-ku, Tokyo, 108-8477, Japan

    Takeshi Terahara

  4. Keio University Health Center, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Tomoyasu Nishimura

  5. Department of Infectious Diseases, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Naoki Hasegawa

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  1. Satoru Shigeno
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  2. Miyu Kadowaki
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  8. Hiroshi Tomoda
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Correspondence to Hiroshi Tomoda or Taichi Ohshiro.

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Shigeno, S., Kadowaki, M., Nagai, K. et al. New polycyclic tetramate macrolactams with antimycobacterial activity produced by marine-derived Streptomyces sp. KKMA-0239. J Antibiot 77, 265–271 (2024). https://doi.org/10.1038/s41429-024-00710-w

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