Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing heterocyclic carbon compound having only o – n – s,...
Patent
1995-07-14
1997-06-10
Lilling, Herbert J.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing heterocyclic carbon compound having only o, n, s,...
C12P 1702, C12P 100, C12P 1500
Patent
active
056374844
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to a method of producing a taxane-type diterpene including taxol which is useful as a therapeutic agent for ovarian cancer, mammary cancer, lung cancer and the like, and a method of obtaining cultured cells which produce the taxane-type diterpene at a high rate.
BACKGROUND ART
Taxol, which is useful as a therapeutic agent for ovarian cancer, mammary cancer, lung cancer and the like, is a taxane-type diterpene identified after being isolated from Taxus brevifolia NUTT, which is a plant belonging to genus Taxus, family Taxaceae and has a complex ester group which is related to its activity. Taxol can be found in all the parts of the plant body of Taxus brevifolia NUTT, but the bark has been reported to exceed all others in its content of the taxol. At present, taxol is collected from a natural or a cultivated plant body, however, the plant belonging to genus Taxus grows slowly, and it takes more than 10 years to grow to a height of 20 cm above the ground, besides the tree dies after its bark is taken off, thus it has been difficult to easily obtain a large amount of taxol. It would be advantageous if a taxane-type diterpene such as taxol and baccatin III which is a precursor of taxol, can be produced by the use of tissue culture, since a large amount of taxol can be easily obtained without cutting down the trees.
As a conventional method of producing taxol by utilizing cultured plant cells, a U.S. patent was issued on a production method utilizing cultured cells of Taxus brevifolia NUTT (U.S. Pat. No. 5,019,504), however, the yield of taxol production described therein is 1-3 mg/l, and that is insufficient for the industrial production. Besides, the production of taxol by the cell culture is unstable and even when a primary cell of high productivity can be obtained by selection, it is difficult to keep its content by subculturing [E. R. M. Wickremesine et al., World Congress on Cell and Tissue Culture (1992)].
On the other hand, as a prior art in the taxol production, a semisynthetic method from baccatin III, which is a precursor in biosynthesis of taxol, is disclosed in the specification of U.S. Pat. No. 5,015,744 issued to Holton et al. By the use of the plant tissue culture, a raw material for the semisynthetic process such as baccatin III can be produced, thus the plant tissue culture can be also utilized for taxol production by the above-mentioned semisynthetic process.
DISCLOSURE OF INVENTION
The first object of the present invention is to provide a simple method of producing a taxane-type diterpene by plant tissue culture.
The second object of the present invention is to provide a method of obtaining cultured cells which produce a taxane-type diterpene at a high rate.
The first invention of the present application is a method of producing a taxane-type diterpene wherein a tissue or a cell of a plant which produces a taxane-type diterpene is cultured in the presence of at least one substance selected from the group consisting of jasmonic acids, compounds containing a heavy metal, complex ions containing a heavy metal, heavy metal ions, amines and antiethylene agents, then the taxane-type diterpene is recovered from the resulting cultures.
The second invention of the present application is a method of producing a taxane-type diterpene wherein a tissue or a cell of a plant which produces a taxane-type diterpene is cultured by controlling the oxygen concentration in a gas phase in a culture vessel to less than the oxygen concentration in the atmosphere, from the initial stage of the culture, or by controlling the dissolved oxygen concentration in a fluid medium which is in contact with the tissue or the cell to less than the saturated dissolved oxygen concentration at that temperature, from the initial stage of the culture, then the taxane-type diterpene is recovered from the resulting cultures.
The third invention of the present application is a method of obtaining cultured cells which produce a taxane-type diterpene at a high rate, wherein cells of a plant w
REFERENCES:
patent: 5015744 (1991-05-01), Holton
patent: 5019504 (1991-05-01), Christen et al.
patent: 5407816 (1995-04-01), Bringi et al.
E.R.M. Wickremesine et al., 1992 World Congress On Cell and Tissue Culture, Development of callus and cell suspension . . . , vol. 28, No. 3, Mar., 1992.
Hara Yasuhiro
Higashi Yosuke
Matsubara Kouichi
Ohnishi Naoto
Suga Chuzo
Lilling Herbert J.
Mitsui Petrochemical Industries Ltd.
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