곰팡이 분리주 MT60109가 생산하는 Phospholipase C 저해물질의 분리

  • Oh, Won-Keun (Cellular Response Modifier Research Unit., Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Hyun-Sun (Cellular Response Modifier Research Unit., Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Chan-Sun (Cellular Response Modifier Research Unit., Korea Research Institute of Bioscience and Biotechnology) ;
  • Ahn, Soon-Cheol (Cellular Response Modifier Research Unit., Korea Research Institute of Bioscience and Biotechnology) ;
  • Ko, Hack-Ryong (Cellular Response Modifier Research Unit., Korea Research Institute of Bioscience and Biotechnology) ;
  • Mheen, Tae-Ick (Cellular Response Modifier Research Unit., Korea Research Institute of Bioscience and Biotechnology) ;
  • Ahn, Jong-Seog (Cellular Response Modifier Research Unit., Korea Research Institute of Bioscience and Biotechnology)
  • 오원근 (생명공학연구소, 세포반응조절 연구Unit) ;
  • 이현선 (생명공학연구소, 세포반응조절 연구Unit) ;
  • 박찬선 (생명공학연구소, 세포반응조절 연구Unit) ;
  • 안순철 (생명공학연구소, 세포반응조절 연구Unit) ;
  • 고학룡 (생명공학연구소, 세포반응조절 연구Unit) ;
  • 민태익 (생명공학연구소, 세포반응조절 연구Unit) ;
  • 안종석 (생명공학연구소, 세포반응조절 연구Unit)
  • Published : 1997.12.01

Abstract

During the screening of inhibitors against phospholipase C (PLC) and the formation of inositol phosphates (IP$_{t}$) at NIH3T3${\gamma}$1 cells from microbial secondary metabolites, we selected a fungal strain MT60109 which was capable of producing an inhibitor. By the taxonomic studies, this fungus was identified as Pseudallescheria sp. MT60109 and an inhibitor of PLC was purified by BuOH extraction and chromatographic techniques from the culture broth of Pseudallescheria sp. MT60109. The inhibitor was identified as thielavin B by the physico-chemical properties and spectroscopic analysis of UV, FAB-MS, $^{1}$H, $^{13}$C-NMR, $^{1}$H-$^{1}$H COSY and HMBC. Thielavin B showed potent inhibitory activity against PLC purified from bovine brain with an IC$_{50}$ of 20 $\mu$M. And it also inhibited the formation of inositol phosphates in platelet-derived growth factor (PDGF) -stimulated NIH3T3${\gamma}$1 cells with an IC$_{50}$ of 20 $\mu$M.

Keywords

References

  1. Science v.244 Studies of inositol phospholipid-specific phospholipase C Rhee,S.G.;Suh,P.G.;Ryu,S.H.;Lee,S.Y.
  2. Science v.233 Studies and perspectives of protein kinase C Nishizuka,Y.
  3. Cancer biology v.3 Drugs active against growth factor and oncogene phosphatidyl-inositol signalling pathways Powis,G.
  4. Drugs of the Future v.18 Inhibitors of phospholipase C Powis,G.
  5. Cancer Research v.52 Selective inhibition of phosphatidylinositol phospholipase C by cytotoxic ether lipid analogues Powis,G.;Seewald,M.J.;Cratas,D.;Modest,E.J.
  6. Nat. Prod. Rep. v.1 Recent advances in the chemistry and biochemistry of inositol phosphates of biological interest Potter,B.V.L.
  7. Tetrahed. Lett. v.32 Structure of a novel phospholipase C inhibitor, vinaxanthone(R009-1450), produce by Penicillium vinaceum Aoki,M.;Itezono,Y.;Shirai,H.;Nakayama,N.;Sakai,A.;Tanaka,Y.
  8. Biochem. Biophys. Acta. v.1175 An inhibitor of inositol-phospholipid-specific phospholipase C Ogawara,H.;Higashi,K.;Manita,S.;Hidaka,M.;Kato,H.;Takenawa,T.
  9. J. Antibiotics v.47 Hispidospermidin, a novel phospholipase C inhibitor produced by Chaletosphaeronema hispidulum(Cda) Moesz NR 7127 Yanagisawa,M.;Sakai,A.;Adachi,K.Sano,T.;Watanabe,K.
  10. J. Antibiotics v.47 Caloporoside, a new inhibitor of phospholipase C from Caloporus dichrous(Fr.) Ryv Weber,W.;Schu,P.;Anke,T.;Velten,R.;Steglich,W.
  11. Planta medica v.62 Inhibition of phospholipase Cγ1 activity by amentoflavone isolated from Selaginella tamariscina Lee,H.S.;Oh,W.K.;Kim,B.Y.Ahn,S.C.;Kang,D.O.;Shin,D.I.;Kim,J.W.;Mheen,T.I.;Ahn,J.S.
  12. Planta medica Inhibition of phospholipase Cγ1 activity by the prenylated flavonoids from Sophora flavenscens Lee,H.S.;Ko,H.R.;Ryu,S.Y.;Oh,W.K.;Kim,B.Y.;Ahn,S.C.;Mheen,T.I.;Ahn,J.S.
  13. Medically important fungi: a guide to identification Larone,D.H.
  14. Compendium of soil fungi v.1 Domsch,K.H.;Gams,W.;Anderson,T.H.
  15. Methods in Enzymol. v.197 Assays of phosphoinositide-specific phospholipase C and purification of isozymes from bovine brain Rhee,S.G.;Ryu,S.H.;Cho,K.S.
  16. Biochem. Mol. Biol. Intern. v.37 Inhibition of PDGF-induced phosphoinositide-turnover by glucopiericidin A Ahn,S.C.;Kim,B.Y.;Park,C.S.;Lee,H.S.;Suh,P.G.;Ryu,S.H.;Rho,H.M.;Rhee,J.S.;Mheen,T.I.;Ahn,J.S.
  17. 약학회지 v.37 능소화의 꽃받침으로부터 protein kinase C 저해물질인 Verbascoside의 분리 및 그 생물활성 이현선;박문수;오원근;안순철;김보연;김환묵;오구택;민태익;안종석
  18. Appl. Microbiol. v.26 Dermatophyte test medium: evaluation with nondermatophytic pathogens Salkin,L.F.
  19. J. Antibiotics v.34 Thielavin A and B, new inhibitors of prostaglandin biosynthesis produced by Thielavia terricola Kitahara,N.;Endo,A.;Furuya,K.;Takahashi,S.