Taxol is one of the most promising anti-cancer drugs currently under investigation. Clinical trials have proven the usefulness of this compound especially in cancers of the breast and ovarian systems. The main factor limiting a more widespread use of taxol is its availability. In nature it is found exclusively in the plant genus Taxus and in particular in the U.S., the wild species Taxus brevifolia (Pacific yew). In this project we seek to investigate those factors in the plant and its microbial environment that influence taxol production. Initially, we will do this using an in vitro system involving inner bark pieces that biosynthesize taxol. This test system has already been proven. We now seek to more completely explore, isolate and identify those factors from endophytic fungi that affect taxol production. Preliminary data unequivocally have shown a positive influence of such compounds as fungal elicitors, gibberellic acid and chloro- choline chloride on taxol production. Also, it is also conceivable that one or more endophytic fungi or bacteria from Taxus are capable of producing taxol or a related taxane. We have been successful in isolating at least 50 fungi from aseptically treated inner bark. We plan to systematically screen these organisms for taxol (taxane) production. Field studies, in vitro production of taxol by a bark reactor, and other biological and chemical factors controlling taxol production will be studied.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA058315-02
Application #
2099010
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1993-05-28
Project End
1996-04-30
Budget Start
1994-05-04
Budget End
1995-04-30
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Montana State University Bozeman
Department
Other Basic Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
City
Bozeman
State
MT
Country
United States
Zip Code
59717
Li, J Y; Strobel, G; Sidhu, R et al. (1996) Endophytic taxol-producing fungi from bald cypress, Taxodium distichum. Microbiology 142 ( Pt 8):2223-6
Strobel, G A; Hess, W M (1996) A scanning electron microscopy study of Taxus leaves as related to taxonomy. Scanning Microsc 10:1111-26
Strobel, G; Yang, X; Sears, J et al. (1996) Taxol from Pestalotiopsis microspora, an endophytic fungus of Taxus wallachiana. Microbiology 142 ( Pt 2):435-40