2000) Furthermore, low Taxol concentrations, comparable to the l

2000). Furthermore, low Taxol concentrations, comparable to the levels we detected in endophyte extracts, did not affect the physiological properties of the membrane (Balasubramanian and Straubinger 1994; Sharma and Straubinger 1994; Bernsdorf et al. 1999; Crosasso et al. 2000; Zhao and Feng 2004). Although these experiments involved artificial membranes, there is also evidence

that fungi can take up non-polar compounds by passive transport and store them in vesicles. For example, Fusarium solani can absorb polyaromatic compounds from the cell culture medium and store them within intracellular compartments with no impact on growth (Verdin et al. 2005). In the endophytes we studied, the accumulation of non-polar taxoid molecules in lipophilic cell structures combined with the high sensitivity of our analytical methods, immunological detection and LC/MS/MS-based multi-reaction monitoring (MRM) ensured that these Torin 1 purchase carry-overs could be detected. After the first and second passages of the fungal cultures, no taxanes could be detected by LC/MS/MS. The fungi were no longer associated with the Taxol source and CYC202 in vitro hence the trace amounts of taxanes detected initially were diluted below the detection limit. Our

results and conclusions therefore offer a satisfactory explanation for the contradictory results in earlier publications, some providing evidence for independent taxane biosynthesis in different endophytic fungi and others lacking this evidence. Acknowledgments U.H. was supported by a pre-doctoral fellowship from the Volkswagen Foundation, Hannover, Germany (AZ.: I/82 754). Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source

are credited. Electronic supplementary selleckchem material Below is the link to the electronic supplementary material. ESM 1 (DOCX 666 kb) References Agger S, Lopez-Gallego F, Schmidt-Dannert C (2009) Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol Microbiol 72(5):1181–1195PubMedCrossRef Balasubramanian SV, Straubinger RM (1994) Taxol–lipid interactions: taxol-dependent effects on the physical properties of model membranes. Biochemistry almost 33:8941–8947PubMedCrossRef Baloglu E, Kingston DGI (1999) Taxane diterpenoids. J Nat Prod 62:1448–1472PubMedCrossRef Bernsdorf C, Reszka R, Winter R (1999) Interaction of the anticancer agent Taxol (paclitaxel) with phospholipid bilayers. J Biomed Mater Res 46:141–149CrossRef Bömke C, Tudzynski B (2009) Diversity, regulation, and evolution of the gibberellin biosynthetic pathway in fungi compared to plants and bacteria. Phytochemistry 70:1876–1893PubMedCrossRef Brown DT (2003) Preclinical and clinical studies of the taxanes. In: Itokawa H, Lee K-H (eds) The genus Taxus.

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