Skip to main content

Investigation of the complex antibiotic INA-5812

Abstract

A concentrate with the antimicrobial activity has been isolated from the culture broth of Streptomyces roseoflavus INA-Ac-5812. Its further fractionation by reversed-phase HPLC has resulted in six fractions. It has been established by MALDI-TOF and ESI-MSn precision mass-spectrometry methods that the main components of the complex antibiotic are several closely related compounds, presumably of a glycopeptide nature. The fraction containing an individual component with a mass of 1845.788 Da has been characterized by UV/Vis absorbance and fluorescence spectra, amino acid analysis, and derivatization with tris(2,6-dimethoxyphenyl)methyl cation. The activity of fractions against pathogenic microbes has been studied. The results allow the supposition that the INA-5812 antibiotic complex is a glyco- or lipoglycopeptide antibiotic of a new type, which is very promising for further study.

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

Abbreviations

CFU:

colony-forming unit

rpHPLC:

reversedphase high performance liquid chromatography

DEAE:

diethylaminoethyl

HRESI-MS:

high-resolution electrospray ionization mass spectrometry

MALDI-TOF:

matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

TFA:

trifluoroacetic acid

References

  1. Shen, B, Cell, 2015, vol. 163, pp. 1297–1300.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Newman, D.J. and Cragg, G.M., J. Nat. Prod., 2016, vol. 79, pp. 629–661.

    CAS  Article  PubMed  Google Scholar 

  3. Brown, E.D. and Wright, G.D, Nature, 2016, vol. 529, pp. 336–343.

    CAS  Article  PubMed  Google Scholar 

  4. Ling, L.L., Schneider, T., Peoples, A.J., Spoering, A.L., Engels, I., Conlon, B.P., Mueller, A., Schaäberle, T.F., Hughes, D.E., Epstein, S., et al, Nature, 2015, vol. 517, pp. 455–459.

    CAS  Article  PubMed  Google Scholar 

  5. Lapchinskaya, O.A., Katrukha, G.S., Terekhova, L.P., Kulyaeva, V.V., Gladkikh, E.G., Pogozheva, V.V., Fedorova, G.B., Mirchink, E.P., Makarova, M.O., Treshchalin, I.D., Isakova, E.B., Ponomarenko, V.I., Pereverzeva, E.R., Abramova, E.A., and Tokareva, N.L., RF Patent no. 2572341, 2016.

    Google Scholar 

  6. Osterman, I.A., Prokhorova, I.V., Sysoev, V.O., Boykova, Y.V., Efremenkova, O.V., Svetlov, M.S., Kolb, V.A., Bogdanov, A.A., Sergiev, P.V., and Dontsova, O.A, Antimicrob. Agents Chemother., 2012, vol. 56, pp. 1774–1783.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Baba, T., Ara, T., Hasegawa, M., Takai, Y., Okumura, Y., Baba, M., Datsenko, K.A., Tomita, M., Wanner, B.L., and Mori, H., Mol. Syst. Biol., 2006, vol. 2, 2:2006.0008.

  8. Topol’yan, A.P., Strizhevskaya, D.A., Slyundina, M.S., Belyaeva, M.A., Ivanova, O.M., Korshun, V.A., Ustinov, A.V., Mikhura, I.V., Formanovskii, A.A., and Borisov, R.S, Mass-Spektrometriya, 2015, vol. 12, pp. 253–258

    Google Scholar 

  9. Topol’yan, A.P., Belyaeva, M.A., Bykov, E.E., Kudan, P.V., Rogozhin, E.A., Strizhevskaya, D.A., Ivanova, O.M., Ustinov, A.V., Mikhura, I.V., Prokhorenko, I.A., Korshun, V.A., and Formanovskii, A.A, Acta Naturae, 2016, vol. 8, pp. 100–107.

    Google Scholar 

  10. Lakey, J.H. and Ptak, M, Biochemistry, 1988, vol. 27, pp. 4639–4645.

    CAS  Article  PubMed  Google Scholar 

  11. Nicolaou, K.C., Boddy, C.N.C., Bräse, S., and Winssinger, N, Angew. Chem, Int. Ed. Engl., 1999, vol. 38, pp. 2096–2152.

    CAS  Article  Google Scholar 

  12. Kahne, D., Leimkuhler, C., Lu, W., and Walsh, C, Chem. Rev., 2005, vol. 105, pp. 425–448.

    CAS  Article  PubMed  Google Scholar 

  13. Timofeeva, A.V., Lapchinskaya, O.A., Stepashkina, E.A., Gladkikh, E.G., Pogozheva, V.V., Baratova, L.A., and Katrukha, G.S, Biotekhnologiya, 2012, no. 4, pp. 45–51.

    Google Scholar 

  14. Tashlitskii, V.N., Tsarev, D.A., and Kaz’mina, E.M, Razrab. Registr. Lekarstv. Sredstv, 2013, no. 1, pp. 38–44.

    Google Scholar 

  15. Spackman, D.H., Stein, W.H., and Moore, S, Anal. Chem., 1958, vol. 30, pp. 1190–1206.

    CAS  Article  Google Scholar 

  16. Timofeeva, A.V., Serebryakova, M.V., Baratova, L.A., and Katrukha, G.S, Biotekhnologiya, 2009, no. 1, pp. 90–95.

    Google Scholar 

  17. Isaacson D.M., in Industrial Microbiotechnology, Kirschbaum, G., Ed., Washington, D.C.: Am. Soc. Microbiol., 1986, pp. 411–418.

  18. Ustyugova, E.A., Timofeeva, A.V., Stoyanova, L.G., Netrusov, A.I., and Katrukha, G.S, Appl. Biochem. Microbiol., 2012, vol. 48, pp. 557–563.

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. P. Tyurin.

Additional information

Original Russian Text © O.A. Lapchinskaya, G.S. Katrukha, E.G. Gladkikh, V.V. Kulyaeva, P.V. Coodan, A.P. Topolyan, V.A. Alferova, V.V. Pogozheva, M.A. Sukonnikov, E.A. Rogozhin, I.A. Prokhorenko, V.A. Brylev, A.M. Korolev, M.S. Slyundina, R.S. Borisov, M.V. Serebryakova, M.V. Shuvalov, A.L. Ksenofontov, L.G. Stoyanova, I.A. Osterman, A.A. Formanovsky, V.N. Tashlitsky, L.A. Baratova, A.V. Timofeeva, A.P. Tyurin, 2016, published in Bioorganicheskaya Khimiya, 2016, Vol. 42, No. 6, pp. 732–740.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lapchinskaya, O.A., Katrukha, G.S., Gladkikh, E.G. et al. Investigation of the complex antibiotic INA-5812. Russ J Bioorg Chem 42, 664–671 (2016). https://doi.org/10.1134/S1068162016060078

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162016060078

Keywords

  • microbial metabolites
  • glycopeptide antibiotics
  • high performance liquid chromatography
  • high-resolution mass spectrometry