Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Rubiflavin G, photorubiflavin G, and photorubiflavin E: Novel pluramycin derivatives from Streptomyces sp. W2061 and their anticancer activity against breast cancer cells


The pluramycin family of antibiotics comprises angucycline compounds derived from actinomycetes that possess anticancer and antibacterial properties. Pluramycins are structurally characterized by two aminoglycosides linked by a carbon-carbon bond next to the γ-pyrone angucycline backbone. Kidamycins (3, 4) and rubiflavins (69) were screened through liquid chromatography–mass spectrometry analysis of the crude extracts of Streptomyces sp. W2061, which was cultured in complex media under phosphate-limiting conditions. Newly isolated rubiflavin G (7) and photoactivated compounds (8, 9) were characterized using exhaustive 1D and 2D nuclear magnetic resonance analysis. The cytotoxicity of kidamycin (3), photokidamycin (4), and photorubiflavin G (8) was determined using two human breast cancer cell lines–MCF7 and MDA-MB-231. Compared to MCF7 cells, MDA-MB-231 cells were more sensitive to the active compounds, and photokidamycin (4) considerably inhibited MCF7 and MDA-MB-231 cell growth (IC50 = 3.51 and 0.66 μM, respectively).

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3


  1. Martin JF, Demain AL. Control of antibiotic biosynthesis. Microbiol Rev. 1980;44:230–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Demain AL, Sanchez S. Microbial drug discovery: 80 years of progress. J Antibiot. 2009;62:5–16.

    Article  CAS  Google Scholar 

  3. van Wezel GP, McDowall KJ. The regulation of the secondary metabolism of Streptomyces: new links and experimental advances. Nat Prod Rep. 2011;28:1311–33.

    Article  PubMed  Google Scholar 

  4. Qin Y, et al. OSMAC strategy integrated with molecular networking discovery peniciacetals A-I, nine new meroterpenoids from the mangrove-derived fungus Penicillium sp. HLLG-122. Bioorg Chem. 2023;130:106271.

    Article  CAS  PubMed  Google Scholar 

  5. Hemphill CFP, et al. OSMAC approach leads to new fusarielin metabolites from Fusarium tricinctum. J Antibiot. 2017;70:726–32.

    Article  CAS  Google Scholar 

  6. Maeda K, et al. A new antitumor substance, pluramycin; studies on antitumor substances produced by Actinomycetes. XI. J Antibiot. 1956;9:75–81.

    CAS  Google Scholar 

  7. Schmitz H, Crook KE Jr., Bush JA. Hedamycin, a new antitumor antibiotic. I. Production, isolation, and characterization. Antimicrob Agents Chemother. 1966;6:606–12.

    CAS  PubMed  Google Scholar 

  8. Kanda N. A new antitumor antibiotic, kidamycin. I. Isolation, purification and properties of kidamycin. J Antibiot. 1971; 24:599–606.

    Article  CAS  Google Scholar 

  9. Jackson M, et al. Altromycins, novel pluramycin-like antibiotics. I. Taxonomy of the producing organism, fermentation and antibacterial activity. J Antibiot. 1990;43:223–8.

    Article  CAS  Google Scholar 

  10. Aszalos A, Jelinek M, Berk B. Rubiflavin, a toxic antitumor antibiotic. Antimicrob Agents Chemother. 1964;10:68–74.

    CAS  PubMed  Google Scholar 

  11. Bililign T, Griffith BR, Thorson JS. Structure, activity, synthesis and biosynthesis of aryl-C-glycosides. Nat Prod Rep. 2005;22:742–60.

    Article  CAS  PubMed  Google Scholar 

  12. Cairns MJ, Murray V. Detection of protein-DNA interactions at beta-globin gene cluster in intact human cells utilizing hedamycin as DNA-damaging agent. DNA Cell Biol. 1998;17:325–33.

    Article  CAS  PubMed  Google Scholar 

  13. Masuma R, Tanaka Y, Tanaka H, Omura S. Production of nanaomycin and other antibiotics by phosphate-depressed fermentation using phosphate-trapping agents. J Antibiot. 1986;39:1557–64.

    Article  CAS  Google Scholar 

  14. Tanaka Y, Fermentation processes in screening for new bioactive substances. In: Omura S, editors. The Search for Bioactive Compounds from Microorganisms. New York: Springer-Verlag; 1992. p. 303–63.

  15. Heo KT, Lee B, Jang JH, Hong YS. Elucidation of the di-C-glycosylation steps during biosynthesis of the antitumor antibiotic, kidamycin. Front Bioeng Biotechnol. 2022;10:985696.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Martin JF, Rodriguez-Garcia A, Liras P. The master regulator PhoP coordinates phosphate and nitrogen metabolism, respiration, cell differentiation and antibiotic biosynthesis: comparison in Streptomyces coelicolor and Streptomyces avermitilis. J Antibiot. 2017;70:534–41.

    Article  CAS  Google Scholar 

  17. Omura S, Tomoda H, Xu QM, Takahashi Y, Iwai Y. Triacsins, new inhibitors of acyl-CoA synthetase produced by Streptomyces sp. J Antibiot. 1986;39:1211–18.

    Article  CAS  Google Scholar 

  18. Andreas Fredenhagen US. The Structures of some products from the photodegradation of the pluramycin antibiotics hedamycin and kidamycin. Helv. Chim. Acta. 1985; 68:391–402.

  19. Tsukahara K, Toume K, Ito H, Ishikawa N, Ishibashi M. Isolation of beta-indomycinone guided by cytotoxicity tests from Streptomyces sp. IFM11607 and revision of its double bond geometry. Nat Prod Commun. 2014;9:1327–28.

    CAS  PubMed  Google Scholar 

  20. Mabit T, et al. Total Synthesis of gamma-indomycinone and kidamycinone by means of two regioselective Diels-Alder reactions. J Org Chem. 2017;82:5710–19.

    Article  CAS  PubMed  Google Scholar 

  21. Ando Y, Maezawa Y, Shimura J, Kitamura K, Matsumoto T, Suzuki K. Toward pluramycins with epoxy side chain: Syntheses of kidamycinone and epoxykidamycinone (saptomycinone H). Chem Asian J. 2020;15:828–32.

    Article  CAS  PubMed  Google Scholar 

  22. Hertweck C, Luzhetskyy A, Rebets Y, Bechthold A. Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork. Nat Prod Rep. 2007;24:162–90.

    Article  CAS  PubMed  Google Scholar 

  23. Williamson RT, McDonald LA, Barbieri LR, Carter GT. In support of the original medermycin/lactoquinomycin A structure. Org Lett. 2002;4:4659–62.

    Article  CAS  PubMed  Google Scholar 

  24. Jiang YJ, et al. Medermycin-type naphthoquinones from the marine-derived Streptomyces sp. XMA39. J Nat Prod. 2018;81:2120–24.

    Article  CAS  PubMed  Google Scholar 

  25. Tatsuta K, Ozeki H, Yamaguchi M, Tanaka M, Okui T, Nakata M. Total synthesis and biological evaluation of unnatural (-)-medermycin [(-)-lactoquinomycin]. J Antibiot. 1991;44:901–2.

    Article  CAS  Google Scholar 

  26. Cai X, et al. Identification of a C-glycosyltransferase Involved in medermycin biosynthesis. ACS Chem Biol. 2021;16:1059–69.

    Article  CAS  PubMed  Google Scholar 

  27. Zhou B, Jiang YJ, Ji YY, Zhang HJ, Shen L. Lactoquinomycin C and D, two new medermycin derivatives from the marine-derived Streptomyces sp. SS17A. Nat Prod Res. 2020;34:1213–18.

    Article  CAS  PubMed  Google Scholar 

  28. Narita M, Asaoka T, Yano K, Kukita K, Yokoi K, Nakajima T. Novel antibiotic SS21020D and production thereof. Japan Patent Office JPS61115081A. 1986.

  29. Nadig H, Séquin U, Bunge RH, Hurley TR, Murphey DB, French JC. Isolation and structure of a new antibiotic related to Rubiflavin A. Helv Chim Acta. 1985;68:953–957.

    Article  CAS  Google Scholar 

  30. Abe N, Enoki N, Nakakita Y, Uchida H, Nakamura T, Munekata M. Deacetylation effect of N,N-dimethylvancosamine in saptomycins D and E. J Antibiot. 1993;46:692–7.

    Article  CAS  Google Scholar 

  31. Abe N, Enoki N, Nakakita Y, Uchida H, Nakamura T, Munekata M. Novel antitumor antibiotics, saptomycins. II. Isolation, physico-chemical properties and structure elucidation. J Antibiot. 1993;46:1536–49.

    Article  CAS  Google Scholar 

  32. Fredenhagen A, Sequin U. The photodeactivation of hedamycin, an antitumor antibiotic of the pluramycin type. J Antibiot. 1985;38:236–41.

    Article  Google Scholar 

  33. Kitamura K, Ando Y, Matsumoto T, Suzuki K. Total synthesis of aryl C-glycoside natural products: Strategies and tactics. Chem Rev. 2018;118:1495–1598.

    Article  CAS  PubMed  Google Scholar 

  34. Bililign T, Hyun CG, Williams JS, Czisny AM, Thorson JS. The hedamycin locus implicates a novel aromatic PKS priming mechanism. Chem Biol. 2004;11:959–69.

    Article  CAS  PubMed  Google Scholar 

Download references


This work was supported by the Basic Science Research Program (NRF 2020R1I1A206871314) of the Ministry of Education, the NRF grant and the KRIBB Research Initiative Program (KGM5292322 and KGM1222312) funded by the Ministry of Science and ICT (MSIT) of the Republic of Korea. We thank the Korea Basic Science Institute (KBSI), Ochang, Korea, for providing the NMR (Bruker).

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Jae-Hyuk Jang, Yong-Yeon Cho or Young-Soo Hong.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, B., Lee, GE., Hwang, G.J. et al. Rubiflavin G, photorubiflavin G, and photorubiflavin E: Novel pluramycin derivatives from Streptomyces sp. W2061 and their anticancer activity against breast cancer cells. J Antibiot 76, 585–591 (2023).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


Quick links