The overall purpose of the investigation is to develop an economic process for the production of taxol, or functionally similar compounds, in bioreactors using plant tissue culture. Taxol is an antitumor drug derived primarily from Taxus brevifolia, the Western Yew. It has excellent confirmed activity against cancer, particularly refractory human ovarian cancers. T. brevifolia is very slow growing and sufficiently rate to seriously limit the supply of the drug. Plant cell and tissue culture has the potential to provide a controlled supply of the drug to meet the needs of clinical trials and subsequent demand if approved for general clinical use. The proposed work is intended to develop the knowledge base in technical areas that are critical to economic bioreactor production of taxol. Key areas of the investigation are selection of high taxane producing cells, prevention of taxane catabolism, protection of cells from any adverse effects of taxanes and mitigation of any metabolic rate limiting steps. The work will be completed within an applied framework that uses bioengineering scale-up criteria to determine areas needed for improvement. In the short-term, the work will form an important foundation for independent programs in development of tissue culture protocols and scale-up in bioreactors. In the longer term, the investigations will identify strategies for induction of taxol biosynthesis and productivity improvements.
|Ma, W; Stahlhut, R W; Adams, T L et al. (1994) Yunnanxane and its homologous esters from cell cultures of Taxus chinensis var. mairei. J Nat Prod 57:1320-4|
|Ma, W; Park, G L; Gomez, G A et al. (1994) New bioactive taxoids from cell cultures of Taxus baccata. J Nat Prod 57:116-22|
|Bitsch, F; Ma, W; Macdonald, F et al. (1993) Analysis of taxol and related diterpenoids from cell cultures by liquid chromatography-electrospray mass spectrometry. J Chromatogr 615:273-80|