Endophytic paclitaxel synthesizers – search and investigation

While the 1990s brought quite an abundance of reports on paclitaxel-producing endophytes, with the discovery of Taxomyces andreanae in 1993 being merely a starting point [1], no conclusive follow-up data on fungal metabolite profile or the genetic background of the biosynthetic pathway leading to paclitaxel is available as yet. Pursuing the idea of a microbial paclitaxel source providing for an inexhaustible supply of this antineoplastic blockbuster, two objectives were established in course of the hereby presented on-going research. The main emphasis was put on the in-depth study of the aforementioned endophyte, with the experimental procedure undertaken on alternative levels. Metabolic level, with detection of paclitaxel and other taxanes being the main goal, and genomic – aiming at revealing the microbial route leading to paclitaxel, encompassing genes encoding for the consecutive biosynthetic enzymes. As no decisive evidence supporting paclitaxel production in Taxomyces andreanae under our experimental conditions has been obtained, a thorough analysis of endophytic extracts aiming at the verification of their presumed antiproliferation activity was taken up. As investigated upon a human ovarian cancer cell line, the fungal extracts conferred a substantial antineoplastic influence. The natural products responsible for the observed proliferation arrest are, as yet, unknown. The second aspect of our pursuit was the study of a relictual conifer, Wollemia nobilis – an ancient tree reported to be host to a myriad of endophytic fungi, including Pestalotiopsis guepinii – a presumed paclitaxel producer [2]. The initiated screening for the endophytes of the pine in question resulted in obtaining several microbial entities. Further experimental steps, aiming at the isolation of taxol-producing specimens are underway.

References: [1] Stierle, A. et al. (1993) Science 260: 214–216. [2] Strobel, G. et al. (1997) Aust. J. Bot. 45: 1037–1082