New strain and method of producing pacilitaxel using said strain

Abstract

The invention relates to a new fungus that could produce taxales mellow-Alternaria alternate var.monosporus ST-026-R CGMCC No.0899. The invention also discloses the method to produce taxales mellow that includes the following steps: cultivating CGMCC 0899 in culture medium to produce and gather taxales mellow in the strain cell and the culture medium. Thus, the taxales mellow could be recycle and purify in the cell and culture medium. It could solve the technology problem of taxales mellow and protect natural resource.

Description

technical field [0001] The invention relates to a new bacterial strain and a method for producing paclitaxel by fermenting the bacterial strain. Background technique [0002] Paclitaxel (Paclitaxel, chemical name 5β, 20-epoxy-1,2α, 4,7β, 10β, 13α-hexahydroxytaxane-11-en-9-one-4,10-diacetate-2 - Benzoate-13[(2'R,3'S)-N-benzoyl-3-phenylisoserine ester]) is one of the best anticancer drugs in the world today, FDA (US Food and Drug Administration Bureau) has been approved for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer and AIDS-related kaposi's sarcoma, with significant efficacy. Due to the unique pharmacological mechanism of paclitaxel (that is, promoting the aggregation of tubulin during cancer cell division, stabilizing microtubules, and finally causing cancer cell apoptosis), it can be used for polycystic kidney disease (Cutoclonal pharmaceuticals company in the United States), vascular restenosis (USA Boston Scientific Company) senile dement...

AI Technical Summary

Problems solved by technology

There are following explorations: (1) chemical semi-synthesis (Holton, R.A, Somoza, C., Kim, H-B., Liang, F., et al., J.Am.Chem.Soc., 1994,116 , 1597; 1994, 116, 1599; Nicolaou, R.C., Yang, z., Liu, J.J., et al., Nature, 1994, 367, 630; Danishefskky, S.J., Masters, et al., Angew.Chem, Int. Ed.Engl., 1995, 34, 1723; Wende, A., Badham NeilF., et al., J.Am.Chem.Soc., 1997, 119, 2755-2757): the United States in early 1996, has canceled the tree The bark extraction method is used to produce paclitaxel, and the chemical semi-synthesis method is used instead. This method is mainly to extract the paclitaxel intermediate 10-deacetyl1-baccatin (10-DAB) in the leaves and bark of yew, and then synthesize it through 2-4 steps of chemical reaction Paclitaxel, although it solves the problem of ecological protection, still needs a large number of plantations to support, which consumes a lot of land and manpower. From a long-term perspective, this method is still not advisable

(2) chemical synthesis (DenisJN, Greene AE, Guenard D, et al., J.Am.Chem.Soc., 1988,110,2917; Kingston DG, Chaudhary AG, Gunatilaka AAL, et al., Tetrahedron Lett. , 1994, 35, 4483; Kanazawa AM, Denis JN, GreeneAE, J.Chem.Soc.Chem Commun, 1994, 2591; SISTI, Nicholas, J., WO 96 / 40667; Zhang Hongjie, CN 1241565A): After more than 20 years Years of hard work, in 1994, the total synthesis of paclitaxel was successful, but the entire chemical reaction required more than 20 steps, the efficiency was too low, and the cost was high, so it did not have the meaning of industrial production

(3) Taxus plant cell tissue culture (Huazhong University of Science and Technology, CN1096820A; Minoru Seki, Chiharu Ohzora, Mayuko Takede, Biotechnology and Bioengineering, Vol.53, Pp.214-219, 1997): This method has a long cultivation cycle and industrial production tougher

(4) Paclitaxel produced by microbial fermentation (Andrea Stierle, Gary Strobel, WO93 / 21338; Nippon Steel Corporation, WO95 / 04154; Novopharm, WO 96 / 32490; Gary strobel, Xianshu Yang, et al., Microbiology, 1996, 142, 435-440; Jianfend Wang, Guiling Li, et al., FEMS Microbiology Letters, 2000, 193, 249-253): The production of paclitaxel by this method is not limited by the scarcity of natural resources and ecological protection, but the currently international patented strain A kind of ubiquitous shortcoming that paclitaxel productive rate is low, is not suitable for industrialized large-scale production

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