Endophytes as alternative paclitaxel sources. Chemistry and genetics of Taxomyces andreanae and the endophytic flora of Wollemia nobilis

Promotie: mw. A. Staniek, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Proefschrift: Endophytes as alternative paclitaxel sources. Chemistry and genetics of Taxomyces andreanae and the endophytic flora of Wollemia nobilis

Promotor(s): prof.dr. O. Kayser

Faculteit: Wiskunde en Natuurwetenschappen

Contact: Agata Staniek, tel. 0048-507 845 052, e-mail: stagagata@gmail.com

Endophytes as alternative paclitaxel sources. Chemistry and genetics of Taxomyces andreanae and the endophytic flora of Wollemia nobilis

The research presented in the thesis of Agata Staniek investigates the potential of endophytes as yet untapped, prolific source of pharmaceutically relevant natural products, with an unequivocal attention focused on paclitaxel, the world’s first billion dollar anticancer blockbuster primarily obtained from Taxus brevifolia. While the search for alternative sources of the powerful antineoplastic agent brought an array of reports on paclitaxel producing endophytes, causing quite a controversy over the past two decades, the world’s market still relies on yew-derived supply of the valuable diterpene.

On one hand, Staniek was striving to dissipate the ambiguity surrounding the very first presumed endophytic paclitaxel producer, Taxomyces andreanae, harboured by the original yew synthesizer of the drug. On the other, she described the isolation and screening of the endophytic flora of an ancient conifer, Wollemia nobilis, in search for other paclitaxel producing specimens. In parallel to metabolic profiling by well-established analytical methods, her research was brought to an alternative, previously unattempted level aiming at revealing the genetic background of paclitaxel biosynthe-sis in the fungal isolates.

Wollemi pine, the aforementioned host of endophytic paclitaxel synthesizers, is an exciting object of investigation per se. Thus consecutive chapters of the thesis describe Stanieks efforts to obtain stable in vitro cultures of Wollemia nobilis, as well as its chemistry.

In conclusion she contends that the answer to the issue of paclitaxel supply crisis might lie within the interplay between the plant hosts (often themselves unique, like the relictual Wollemi pine) and their microbial inhabitants, under evolutionary and environmental control.