Structurally diverse metabolites from the rare actinobacterium Saccharothrix xinjiangensis

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. 1.

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

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  3. 3.

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

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  8. 8.

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

    CAS  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  15. 15.

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

    Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  22. 22.

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

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

Download references

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.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Joachim Wink.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

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

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Babadi, Z.K., Sudarman, E., Ebrahimipour, G.H. et al. Structurally diverse metabolites from the rare actinobacterium Saccharothrix xinjiangensis. J Antibiot 73, 48–55 (2020). https://doi.org/10.1038/s41429-019-0223-7

Download citation

Further reading