Mitsui Chemicals, Inc.

Mitsui Petrochemical Industries, Ltd.

Chuzo Suga

Yasuhiro Hara

Yukihito Yukimune

Homare Tabata

Yosuke Higashi

Kouichi Matsubara

Naoto Ohnishi

Method of producing a taxane-type diterpene and a method of obtaining cultured cells which produce the taxane-type dilterpene at a high rate

This invention relates to a method of producing a taxane-type diterpene(s) wherein tissues or cells of a plant which produces taxane-type diterpene(s) is cultured in the presence of at least one 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, a method of producing a taxane-type diterpene wherein the tissues or the cells of the plant are 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, a method of producing a taxane-type diterpene wherein the tissue or the cell of the plant is cultured in a culture vessel, while oxygenic gas containing 0.03-10% of carbon dioxide is used as aeration gas to be introduced to the vessel, and a method of obtaining highly productive cultured cells for the taxane-type diterpene wherein cultured cells of the plant which produces the taxane-type diterpene are separated into a plurality of layers according to the difference in their specific gravities, and the cells contained in at least one layer are cultured, then highly productive cultured cells for the taxane-type diterpene are selected from among those cultured cells. The present invention allows industrial production of a taxane-type diterpene such as taxol which is useful as a therapeutic agent for cancer.

Method of producing a taxane-type diterpene and a method of obtaining

This invention provides for a method for producing secondary metabolites of higher plants, such as Lithospermum erythrorhizon, Coptis japonica, and Nicotinia tabacum, by suspension cultures of a mass of undifferentiated cells (callus). The cultures are carried out in at least two stages in liquid media. The first stage culturing is carried out in a liquid medium conventionally used for the tissue culture of plants, which contains indispensably inorganic substances and carbon sources and, additionally, phytohormones, vitamins and/or amino acids. While, the second stage culturing is carried out in another liquid medium, of which the concentration of at least one of the constituents is substantially varied, namely decreased or increased, from the first stage liquid medium. According to such two stage liquid medium cultures, the productivity of the second metabolites, such as shikonin, berberine and nicotine, are significantly increased, even though the rate of cell growth in the second stage is relatively low.

Method for producing secondary metabolites of plants

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Kuga-gun, Japan

Chuzo Suga