Korean Journal of Microbiology (미생물학회지)

The Microbiological Society of Korea (한국미생물학회)
권호 표지

Chemical Characteristics and Biological Activities of Herbimycin A and Dihydroherbimycin A Produced by a Soil Isolate Streptomyces sp. AO-0511

Streptomyces sp. AO-0511이 생산하는 Herbimycin A 및 Dihydroherbimycin A의 이화학적 특성 및 생물 활성

  • 장흥배 (단국대학교 첨단과학대학 미생물학) ;
  • 김세찬 (단국대학교 첨단과학대학 미생물학) ;
  • 김재헌 (한국 폴리텍 바이오대학 품질관리과)
  • Published : 2006.03.01
Download PDF
⟨ Previous Next ⟩

Abstract

A streptomycete strain was isolated from the soil samples from Korea. The chemotaxonomy and 16S rDNA sequencing confirmed that the strain belonged to the genus Streptomyces and we named it Streptomyces sp. AO-0511. Two antibiotics, herbimycin A and dihydroherbimycin A produced by this strain were tested for their physico-chemical and biological characteristics. Both compounds were stable under acidic pH. Dihydroherbimycin A was more heat-stable and polar compared with herbimycin A. Only weak antibacterial activities were detected against Bacillus subtilus ATCC 6633 and Micrococcus luteus ATCC 9341. However, herbimycin A and dihydroherbimycin A showed strong inhibitory activities on lung cancer cells (A549 cells) and leukemia cells (HL-60). The cytotoxicity was determined using L5178Y and P388 cell lines. The results showed that herbimycin A and dihydroherbimycin A had lower toxic effects on the cells compared with the standard compounds, comptothecin and cyclosporin A. Therefore, both compounds could be good candidates for the development of new anticancer drugs.

한국 토양에서 방선균주를 분리하고 화학 분류 및 16S rDNA 염기서열을 통하여 Streptomyces 속 균주임을 알아내고 Streptomyces sp. AO-0511로 명명하였다. 이 균주가 생산하는 herbimycin A 및 dihydroherbimycin A의 몇 가지 이화학적 성질과 생물 활성을 측정하였다. 두 물질은 모두 산성 조건에서 안정성을 나타냈으며, dihydroherbimycin A는 herbimycin A에 비해 상대적으로 높은 열 안정성을 지니며 극성 또한 높은 물질로서 TLC 상의 Rf간이 낮았다. Herbimycin A와 dihydroherbimycin A는 모두 Bacillus subtilis ATCC 6633 및 Micrococcus luteus ATCC 9341에 대하여 약한 저해 활성을 나타내었고, 다른 미생물에 대해서는 저해 활성을 나타내지 앓았다. 항암 활성에 있어서 두 물질은 폐암 세포인 AS49세포와 백혈병 세포인 HL-60세포에 대해서 강력한 중식 저해 활성을 나타내었다. L5178Y및 P388세포를 사용하여 세포 독성을 측정하였다. 그 결과 두 물질은 대조 물질인 camptothecin에 비해서 항암 활성을 가지면서도 비교적 안전한 물질임을 알려 주고 있다.

Keywords

References

  1. Bendich, A., L.J. Machlin, O. Scadurra, G.W. Burton, and D.D.M. Wayner. 1986. The antioxidant role of vitamin C. Adv. Free Radical Biol. Med. 2, 419-444 https://doi.org/10.1016/S8755-9668(86)80021-7
  2. Bezombes, C., I. Plo, V.M. Mas, A. Quillet-Mary, A. Negre-Salvayre, G. Laurent, and J. Jaffrezou. 2001. Oxidative stressinduced activation of Lyn recruits sphingomyelinase and is requisite for its stimulation by Ara-C. FASEB J. 15, 1583-1588 https://doi.org/10.1096/fj.00-0787fje
  3. Buchner, R.E., and N.E. Gibbons. 1974, Bergey's Manual of Determinative Bacteriology, 8th ed., 724-829
  4. Fleming, A.B, K. Haverstick and W.M. Saltzman. 2004. In vitro cytotoxicity and in vivo distribution after direct delivery of PEGcamptothecin conjugates to the rat brain. Bioconjug. Chem. 15, 1364-1375 https://doi.org/10.1021/bc034180o
  5. Hotta, K and S, Horinouchi. 1994. バイオサイエンスと放 線菌. 醫藥出版社(日本, 東京). pp. 43-80
  6. Iwai, Y., A. Nakagawa, N. Sadakane, and S. Omura. 1980. Herbimycin B, a new benzoquinoid ansamycin with anti-TMV and herbicidal activities. J. Antibiotics 33, 1114-1119 https://doi.org/10.7164/antibiotics.33.1114
  7. Kalakoutskii, L.V. and N.S. Agre. 1976. Comparative aspects of development and differentiation in actinomycetes. Bacteriol. Rev. 40, 469-524
  8. Lechevalier, H.A. and M.P. Lechevalier. 1981. Chapter 147. Introduction to the order Actinomycetales. pp. 1915-1922. In The Prokaryotes. A handbook on habitats, isolation, and identification of bacteria, vol II. eds. Starr, M.P., H. Stolp, H.G. Trueper, A. Balowa and H.G. Schlegel. Springer Verlag Berlin Heidelberg
  9. Lin, L.Z., G. Blasko, and G.A. Cordell. 1988. Proton NMR analysis of herbimycins and dihydroherbimycins. J. Nat. Prod. 51, 1161-1165 https://doi.org/10.1021/np50060a018
  10. Mancini, M., B.O. Anderson, E. Caldwell, M. Sedghinasab, P.B. Paty, and D.M. Hockenbery. 1997. Mitochondrial proliferation and paradoxical membrane depolarization during terminal differentiation and apoptosis in a human colon carcinoma cell line. J.Cell Biol. 138, 449-469 https://doi.org/10.1083/jcb.138.2.449
  11. Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival : application to proliferation and cytotoxicity assays. J. Immunol. Methods. 65, 55-63 https://doi.org/10.1016/0022-1759(83)90303-4
  12. Nomomura, H., 1974, Key for classification and identification of 485 species of Streptomyces included in ISP. J. Ferment. Technol., 52, 78-94
  13. Ogino, S., K. Tsuruma, T. Uehara, and Y. Nomura. 2004. Herbimycin A abrogates nuclear factor-$\kappa$B activation by interacting preferentially with the I$\kappa$B kinase subunit. Mol. Pharmacol. 65, 1344-1351 https://doi.org/10.1124/mol.65.6.1344
  14. Omura, S., A. Nakagawa, and N. Sadakane. 1979. structure of herbimycin, a new ansamycin antibiotic. Tetrahedron Lett. 44, 4323- 4326
  15. Omura, S., Y. Iwai, Y. Takashi, N. Sadakane, and A. Nakagawa. 1979. Herbimycin A, a new antibitotic produced by a strain of Streptomyces. J. Antibiotics 32, 255-261 https://doi.org/10.7164/antibiotics.32.255
  16. Shibata, K., S. Satsumabayashi, A. Nakagawa, and S. Omura. 1986. The structure and cytocidal activity of herbvimycin C. J.Antibiotics 39, 415-423 https://doi.org/10.7164/antibiotics.39.415
  17. Shirling, E.B. and D. Gottlieb. 1966. Method for characterization of Streptomyces species. Int. J. System Bacteriol. 16, 313-340 https://doi.org/10.1099/00207713-16-3-313
  18. Turturro, F., M.D. Arnold, A.Y. Frist, and K. Dulford. 2002. Model of inhibition of the NPM-ALK kinase activity by herbimycin A. Clin. Cancer Res. 8, 240-245
  19. Uehara, Y., M. Hori, T. Takeuchi, and H. Umezawa. 1986. Phenotypic change from transformed to normal induced by benzoquinoid ansamycins accompanies inactivation of $p60^{src}$ in rat kidney cells infected with Rous sarcoma viruse. Mol. Cell. Biol.. 6, 2197-2206