Enhanced production of taxol and taxanes by cell cultures of taxus species

Abstract

This invention provides methods whereby taxol, baccatin III, and other taxol-like compounds, or taxanes, can be produced in very high yield from all known Taxus species, e.g., brevifolia, canadensis, cuspidata, baccata, globosa, floridana, wallichiana, media and chinensis . Particular modifications of culture conditions (i.e., media composition and operating modes) have been discovered to enhance the yield of various taxanes from cell culture of all species of Taxus . Particularly preferred enhancement agents include silver ion or complex, jasmonic acid (especially the methyl ester), auxin-related growth regulators, and inhibitors of the phenylpropanoid pathway, such as 3,4-methylenedioxy-6-nitrocinnamic acid. These enhancement agents may be used alone or in combination with one another or other yield-enhancing conditions. While the yield of taxanes from plant cell culture of T. chinensis is particularly enhanced by use of one or more of these conditions, yield of taxanes for all Taxus species has been found to benefit from use of these conditions.

1 .- 62 . (canceled) 
     
     
         63 . A method for producing paclitaxel and other taxanes from cell culture of a  Taxus  species comprising: cultivating in suspension culture, in a first medium developed for a growth phase and then in a second medium developed for a product formation phase, cells of a  Taxus  species derived from callus and/or suspension cultures, and recovering said paclitaxel and other taxanes from said cells, wherein said step of cultivating is carried out in the presence of 0.03% to 15% v/v of carbon dioxide in the gas phase in equilibrium with at least one of said first medium and said second medium.