Structurally diverse metabolites from the rare actinobacterium Saccharothrix xinjiangensis

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Abstract

The bioassay-guided fractionation from cultures of the actinobacterium Saccharothrix xinjiangensis Act24Zk, collected from the Caspian Sea beach in Iran led to the isolation of three new compounds, caerulomycin M (1), saccharopyrone (2), and saccharonoic acid (3), together with the known compound, caerulomycin A (4). Their structures were elucidated from HR-ESIMS and 1D and 2D NMR data. Compound 2 displayed moderate cytotoxic activity against the human cervix carcinoma HeLa cells KB3.1 with an IC50 value of 5.4 µM.

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References

  1. 1.

    Banin E, Hughes D, Kuipers OP. Bacterial pathogens, antibiotics and antibiotic resistance. FEMS Microbiol Rev. 2017;41:450–2.

  2. 2.

    Ibeyaima A, Dwivedi AK, Saini N, Gupta S, Sarethy IP. Saccharothrix sp. TD-093 from the Thar desert, India: metabolite fingerprinting of antimicrobial compounds and in silico analysis. Curr Microbiol. 2017;74:334–3.

  3. 3.

    Dewi TK, Agustiani D, Antonius S. Secondary metabolites production by Actinomycetes and their antifungal activity. KnE Life Sci. 2017;3:256–64.

  4. 4.

    Bahri A, Moazamian E, Azarpira N. Identification, isolation and evaluation of Persian Gulf actinomycetes as candidates of cytotoxic metabolites against breast cancer. Multidiscip Cancer Investig. 2017;1:10–4.

  5. 5.

    Van der Meij A, Worsley SF, Hutchings MI, van Wezel GP. Chemical ecology of antibiotic production by actinomycetes. FEMS Microbiol Rev. 2017;41:392–416.

  6. 6.

    Lu S, Nishimura S, Ito M, Tsuchida T, Kakeya H. Isolation and structure elucidation of cytotoxic saccharothriolides D to F from a rare actinomycete Saccharothrix sp. and their structure–activity relationship. J Nat Prod. 2016;79:1891–5.

  7. 7.

    Boubetra D, Zitouni A, Bouras N, Mathieu F, Lebrihi A, Schumann P, et al. Saccharothrix hoggarensis sp. nov., an actinomycete isolated from Saharan soil. Int J Syst Evol Microbiol. 2013;63:549–53.

  8. 8.

    Solecka J, Zajko J, Postek M, Rajnisz A. Biologically active secondary metabolites from Actinomycetes. Cent Eur J Biol. 2012;7:373–90.

  9. 9.

    Lu S, Nishimura S, Ito M, Kato T, Kakeya H. Precursor-directed in situ synthesis of saccharothriolides G and H by the actinomycete Saccharothrix sp. A1506. J Antibiot. 2017;70:718.

  10. 10.

    Zhang XG, Liu ZY, Liu JW, Zeng YL, Guo GJ, Sun QY. Antitumor activity of a Rhodococcus sp. Lut0910 isolated from polluted soil. Tumor Biol. 2017;39:10104283177116611.

  11. 11.

    Wang X, Tabudravu J, Jaspars M, Deng H. Tianchimycins A–B, 16-membered macrolides from the rare actinomycete Saccharothrix xinjiangensis. Tetrahedron. 2013;69:6060–4.

  12. 12.

    Lu S, Nishimura S, Hirai G, Ito M, Kawahara T, Izumikawa M, et al. Saccharothriolides A–C, novel phenyl-substituted 10-membered macrolides isolated from a rare actinomycete Saccharothrix sp. Chem Commun. 2015;51:8074–7.

  13. 13.

    Kinoshita N, Igarashi M, Ikeno S, Hori M, Hamada M. Saccharothrix tangerinus sp. nov., the producer of the new antibiotic formamicin: taxonomic studies. Actinomycetologica. 1990;13:20–31.

  14. 14.

    Hu YT, Zhou PJ, Zhou YG, Liu ZH, Liu SJ. Saccharothrix xinjiangensis sp. nov., a pyrene-degrading actinomycete isolated from Tianchi Lake, Xinjiang, China. Int J Syst Evol Microbiol. 2004;54:2091–4.

  15. 15.

    Divekar PV, Read G, Vining LC. Caerulomycin, a new antibiotic from Streptomyces caeruleus Baldacci. II. Struct Can J Chem. 1969;45:1215.

  16. 16.

    Dutton GGS, Merrifield EH, Laffite C, Pratviel-Sosa F, Wylde R. Comparative NMR study of rhamnobioses—applications. Org Magn Reson. 1982;20:154–8.

  17. 17.

    Lahoum A, Sabaou N, Bijani C, Bouras, N, Pont F, Snini SP et al. Antimicrobial activities of novel bipyridine compounds produced by a new strain of Saccharothrix isolated from Saharan soil. Saudi Pharma J. 2018. https://doi.org/10.1016/j.jsps.

  18. 18.

    Schäberle TF. Biosynthesis of α-pyrones. J Org Chem. 2016;12:571–88.

  19. 19.

    Sucipto H, Sahner JH, Prusov E, Wenzel SC, Hartmann 0RW, Koehnke J, et al. In vitro reconstitution of α-pyrone ring formation in myxopyronin biosynthesis. Chem Sci. 2015;6:5076–85.

  20. 20.

    Sucipto H, Wenzel SC, Müller R. Exploring chemical diversity of α-pyrone antibiotics: Molecular basis of myxopyronin biosynthesis. ChemBioChem. 2013;14:1581–9. https://doi.org/10.1002/cbic.201300289.

  21. 21.

    Stahl M, Schopfer U, Frenking G, Hoffmann RW. Assignment of relative configuration to acyclic compounds based on 13C NMR shifts. A density functional and molecular mechanics study. J Org Chem. 1996;61:8083–8.

  22. 22.

    Hoffmann RW. Flexible molecules with defined shape—conformational design. Angew Chem. 1992;104:1147. Angew. Chem., Int. Ed. Engl. 1992;31:1124.

  23. 23.

    Schwecke T, Aparicio JF, Molnár I, König A, Khaw LE, Haydock SF, et al. The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin. Proc Natl Acad Sci USA. 1995;92:7839–43.

  24. 24.

    Xue Y, Zhao L, Liu HW, Sherman HW. A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: architecture of metabolic diversity. Proc Natl Acad Sci USA. 1998;95:12111–6.

  25. 25.

    Akhmedov NG, Gannett PM, Wu B, Cummings MM, Train BC. A conformational NMR analysis of methymycin aglycones: complete and unambiguous assignments of stereochemically diverse glycosylated methymycin analogs by 1D and 2D NMR techniques and molecular modeling. Magn Res Chem. 2013;51:156–67.

  26. 26.

    Funk A, Divekar PV. Caerulomycin, a new antibiotic from Streptomyces caeruleus Baldacci: I. production, isolation, assay, and biological properties. Can J Microbiol. 1959;5:317–21.

  27. 27.

    Shimkets LJ, Dworkin M, Reichenbach H. The prokaryotes: a handbook on the biology of bacteria, 7, New York: Springer; 2006, p. 31‒115.

  28. 28.

    Nakae K, Kurata I, Kojima F, Igarashi M, Hatano M, Sawa R. Sacchathridine A, a prostaglandin release inhibitor from Saccharothrix sp. J Nat Prod. 2013;76:720–2.

  29. 29.

    Surup F, Pommerrehne K, Schroers HJ, Stadler M. Elsinopirins A–D, decalin polyketides from the ascomycete Elsinoё pyri. Biomolecules. 2018. https://doi.org/10.3390/biom8010008.

  30. 30.

    Chepkirui C, Sum WC, Cheng T, Matasyoh JC, Decock C, Stadler M. Aethiopinolones A–E, new pregnenolone type triterpenes from the East African basidiomycete Fomitiporia aethiopica. Molecules. 23:369. https://doi.org/10.3390/molecules23020369.

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Acknowledgements

We thank C. Risdian for assistance in the identification of bacterial strain Act24Zk, A. Gollasch and S. Karwehl for measuring the mass spectra, as well as C. Kakosche for recording NMR spectra and W. Collisi for conduction of bioassays.

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Correspondence to Joachim Wink.

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Babadi, Z.K., Sudarman, E., Ebrahimipour, G.H. et al. Structurally diverse metabolites from the rare actinobacterium Saccharothrix xinjiangensis. J Antibiot (2019) doi:10.1038/s41429-019-0223-7

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