Studies on Xanthine Oxidase Inhibitor Produced from Aspergillus sp. F184

Aspergillus sp. F184가 생산하는 Xanthine Oxidase 저해제에 관한 연구

  • Published : 2000.04.01

Abstract

Aspergillus sp. F184 was isolated from soil for the development of new xanthine oxidase inhibitor. This xanthine oxidase inhibitor was sequentially purified by filtration, HP-20 adsorption column chromatography, ethyl acetate extraction, silica gel column chromatography and crystallization, and was named as YUX 104. YUX 104 was identified to be 5,6-epoxy-2-hydroxy-3-methyl-2-cyclohexene-1,4-dione(terreic acid) by NMR and mass spectroscopic sudies.

통풍과 oxygen free radical의 독성에 관여하는 xanthine oxidase에 대한 새로운 저해물질의 탐색 및 개발을 목적으로 본 연구에서 선택분리한 Aspergillus sp. F184가 생산하는 저해물질을 분리.정제하고 구조를 결정하였으며 효소저해활성을 조사하였다. 본 균주를 배양 후 배양액을 여과하여 균체와 배양액을 분리하고 균체를 acetone으로 추출하고 감압농축하고 남은 수용액층을 배양액과 합쳐 HP-20 adsorption column chromatography, ethyl acetate 추출, silica gel column chromatography, 결정화 등을 실시하여 xanthine oxidase에 대한 저해물질을 분리, 정제하였다. 본 저해물질의 구조를 NMR 및 MS 스펙트럼을 측정하여 분석한 결과 5,6-epoxy-2-hydroxy-3-methyl-2-cyclohexene-1,4-dione으로서 terreic acid로 동정되었다. Terreic acid의 xanthine oxidase에 대한 저해활성을 조사한 결과 IC50가 1.1$\times$10-7M로서 기존의 저해제인 allopurinol과 유사하였다. 이에 terreic acid에 의한 xanthine oxidase 저해활성은 보고된 바가 없기에 새로운 통풍치료제로서의 가능성이 있음을 보고한다.

Keywords

References

  1. Bio-chem. J. v.89 Some properties of xan-thine-oxygen oxidoreductase isolated from pig liver Brumby P.E.;V. Massey
  2. Department of food and biotechnology Studies on the purification of the xanthine oxidase inhibitor from Streptomyces sp;YU-101 Cho D.Y.
  3. Biochem. J. v.126 The regulation of rat liver xanthine oxidase Corte E.D.;F. Strirpe
  4. Bio-chem. Pharm v.15 Metabolic studies of allopurinol, an inhibitor of xanthine oxidase Elion G.B.;K. Aylene;H.H. George
  5. The Pharmacological Basis of Therapeutics (8th ed.) v.2 Gilman A.G.;W.R. Theodore;S.N. Alan;P. Taylor
  6. Gastroenterology v.81 Role of superoxide radicals in intestina;Ischemia Granger D.N.;G. Rutili;J.M. McCord
  7. J. Clin. Invest v.83 Role of Reactive Oxygen Species in Reperfusion injury of the rabbit lung Kennedy T.P.;N.V. Rao;C. Hopkins;L. Pennington;E. Tol-ley;J.R. Hoidal
  8. J. Biol. Chem v.244 The prepara-tion and properties of deflavo xanthine oxidase Komai H.;M. Vincent;P. Graham
  9. J. Biol. Chem v.244 Studies on milk xanthine oxidase Massey V.;E.B. Philip;K. Hirochika
  10. J. Biol. Chem v.243 Preparation of bovine xanthine oxidase and the subunit structues of some iron flavoproteins Nelson C.A.;H. Philip
  11. Biochim. Biophy. Acta v.73 Studies on a hypoxanthine oxidase from bovine small intenstine Roussos G.G.
  12. J. Biol. Chem v.244 The regulation of rat xanthine oxidase conversion in vitro of enzyme activity from dehydrogenase (type D) to oxidase (type O) Stripe F.;C.E. Della
  13. Arch. Biochem. Biophys v.258 Purification of xan-thine dehydrogenase from rat liver;A rapid procedure with high enzyme yields Suleiman S.A.;J.B. Stevens
  14. Jpn. J. Antibiot v.33 Studies on terreic acid Yamamoto H.;K. Moriyama;H. Jinnouchi;K. Yagish-ita
  15. Identification mannual for fungi from utility poles in the eastern united states Wang C.J.K.;R.A. Zabel