Production and Purification of tazane Derivatives from the Plane Cell Cultures of Taxus Chinensis in Large-scale Process

식물세포 Taxus chinensis 의 대량 배양액으로부터의 Taxane 유도체 생산 및 정체

  • 김진현 ((주) 삼양제넥스 생명공학연구소)
  • Published : 2000.08.01

Abstract

Taxiods inclusive paclitaxel were produced isolated and purified from plant cell cultures of Taxus chinensis in large-scale process. their structures were elucidated by spectroscopic analyses. These compounds were exactly identical as those in previous studies from the other biomasses of Taxus chinensis and also other species. Also the concentrations of these compounds were compared with the concentration of the paclitaxel in various batches of plant cell cultures. As paclitaxel concentration increased at the end of cell cultures. the concentrations of the other paclitaxel derivatives decreased. The profile of these taxoids production can provide information for better understanding of structure-activity relationships and biosynthesis Importantly it can be utilized as an useful parameter for the quality control of paclitaxel production.

Taxus chinensis 식물세포 배양에 의한 paclitaxel대량 생산의 경우 biomass내 paclitaxel이외에 다른 많은 유도체들이 확 인 되었다. 이를 목표 물질로 선정하여 Prep-LC를 이용하여 분리/정제하고 NMR, MS 등으로 화학구조분석을 하여 이들 물질들에 대한 동정을 하였다. 또한 Taxus chinensis 식물세포 배양에 의한 paclitaxel 대량 생산의 경우 paclitaxel 생산량에 따른 여러가지 유도체들의 생산 경향을 조사하였으며, paclitaxel의 생산량이 증가할 수록 유도체들의 생산량은 상대 적으로 감소함을 알 수 있었다. 이러한 연구는 결국 paclitaxel 이외의 새로운 유용성분 및 전구체 확인, 분리/정제 방법의 개발, paclitaxel 생산에서의 품질관리에 유용하게 사용되어 질 수 있다.

Keywords

References

  1. Nature v.368 Taxol Inhibits Progression of Congenital Polycystic Kidney Disease Woo, D.D.L.;S.Y.P. Miao;J.C. Pelayo;A.S. Woolf
  2. Nature v.227 Promotion of Microtubule Assembly in vitro by Taxol Schiff, P.B.;J. Fant;S.B. Horwitz
  3. J. Am. Chem. Soc. v.93 The Isolation and Structure of Taxol, A Novel Antileukemic and Antitumor Agent from Taxus brevifolia Wani, M.C.;H.L. Taylor;M.E. Wall;P. Coggon;A.T. Mcphail
  4. Appl. Biochem. Biotech. v.54 Taxol(Paclitaxel); Strategies to Increase the Supply of A New Anticancer Drug Stull, D.P.;T.A. Scales;R. Daughenbaugh;N.A. Jans;D.T. Bailey
  5. U.S.Pantent, 5,871,979 Method for Mass Production of Taxol by Semi-Continuous Culture with Taxus chinensis Cell Culture Choi, H.K.;T.L. Adams;R.W. Stahlhut;S.I. Kim;J.H. Yun;B.K. Song;J.H. Kim;S.S. Hong;H.S. Lee
  6. U.S. Patent, 5,900,979 Method for Purifying Taxol from Taxus Biomass Hong, S.S.;B.K. Song;J.H. Kim;C.B. Lim;H.S. Lee;K.W. Kim;I.S. Kang;H.B. Park
  7. J. Nat. Prod. v.55 ¹H-and ¹³C-NMR Assignments for Taxol, 7-Epi-taxol, and Cephalomannine Chmurny, G.N.;B.D. Hilton;S. Brobst;S.A. Look;K.M. Witherup;J.A. Beutler
  8. Taxol Derivatives, PCT Publication WO 93/21173 Gunawardana, G.P.;L.L. Klein;J.B. McAlpine
  9. J. Nat. Prod. v.50 Taxol and Derivatives : A Biogenetic Hypothesis Voegelein, F.G.;D. Guenard;P. Potier
  10. Pharm. Res. v.12 A New Large-Scale Process for Taxol and Related Taxanes from Taxus brevifolia Rao, K.V.;J.B. Hanuman;C. Alvarez;M. Stoy;J. Juchum;R.M. Davies;R. Baxley
  11. J. Chem. Soc., Chem. Commun. Novel Chemistry of Taxol. Retrosynthetic and Synthetic Studies Nicolaou, K.C.;P.G. Nantermet;H. Ueno;R.K. Guy
  12. J. Nat. Prod. v.57 New Bioactive Taxoids from Cell Cultures of Taxus baccata Ma, W.;G.L. Park;G.A. Gomez;M.H. Mieder;T.L. Adams;J.S. Aynsley;O.P. Sahai;R.J. Smith;R.W. Stahlhut;P.J. Hylands
  13. Pharm. Res. v.10 Taxol and Related Taxanes. I.Taxanes of Taxus brevifolia Bark Rao, K.V.
  14. J. Nat. Prod. v.44 19-Hydroxybaccatin III, 10-Deacetylcephalomannine, and 10-Deacetyltaxol: New Antitumor Taxanes from Taxus wallichiana McLaughlin, J.L.;R.W. Miller;G.R. Powell;C.R. Smith
  15. J. Nat. Prod. v.57 Yunnanxane and Its Homologous Esters from Cell Cultures of Taxus chinensis var.mairei Ma, W.;R.W. Stahlhut;T.L. Adams;G.L. Park;W.A. Evans;S.G. Blumenthal;G.A. Gomez;M.H. Nieder;P.J. Hylands
  16. Tetrahedron v.52 Microbial Transformation of Taxoids : Selective Deacetylation and Hydroxylation of 2(, 5(,10(,14(-Tetra-acetoxy-4-(20),11-Taxadiene by the Fungus Cunninghamella echinulata Hu, S.;X. Tian;W. Zhu;Q. Fang
  17. Tetrahedron v.51 Taxuspines Esimilar-to-H and J, New Taxoids from the Japanese Yew Taxus cuspidate Kobayashi, J.;A. Inubushi;H. Hosoyama;N. Yoshida;T. Sasaki;H. Shigemori
  18. J. Pharm. Exp. Therapeutics v.242 Taxol is Converted to 7-Epitaxol, A Biologically Active Isomer, in Culture Medium Ringel, I.;S.B. Horwitz
  19. J. Chem. Soc., Chem. Commun. Cephalomannine; A New Antitumor Alkaloid from Cephalotaxus mannii Powell, R.G.;R.W. Miller;C.S. Smith