Taxomyces andreanae: a presumed paclitaxel producer demystified?
The 1990s brought an abundance of reports on paclitaxel-producing endophytes, initially heralded as a discovery having tremendous implications for cancer therapy. As the vision of large-scale fermentation tanks producing vast quantities of relatively inexpensive paclitaxel and novel taxanes has faded and has been replaced by controversial silence, we carried out an in-depth investigation of Taxomyces andreanae - the very first presumed endophytic synthesizer of the diterpenoid. On one hand, metabolic profiling by means of chromatographic, spectroscopic and immunoenzymatic techniques predominant in literature was taken up. On the other, the experimental procedure was brought to an alternative, previously unattempted level aiming at revealing the genetic background of paclitaxel biosynthesis in the endophyte. The profound PCR-based screening for taxadiene synthase (TXS) - a gene unique to the formation of the primary taxane-skeleton, as well as phenylpropanoyl transferase (BAPT) encoding for the catalyst of the final acylation of the core structure rendering the ultimate efficacy of the drug, confirmed the molecular blueprint for paclitaxel biosynthesis to be an inherent genetic trait of the endophyte. However, as the thorough metabolic analysis of Taxomyces andreanae commercial isolate brought no confirmation of endophytic paclitaxel production even after considerable up-scaling endeavors, we postulate that proclaiming the strain "a fungus factory for Taxol" might have been premature.
Staniek
Agata
A
Pharmaceutical Biology Department, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands.
Woerdenbag
Herman J
HJ
Kayser
Oliver
O
D000215:Acylation; D000972:Antineoplastic Agents, Phytogenic / Q000096:biosynthesis*; D005658:Fungi / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D007535:Isomerases / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000096:biosynthesis*; D020946:Taxus / Q000382:microbiology; D014166:Transferases / Q000235:genetics / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D014166:Transferases; D007535:Isomerases; C095926:taxa-4(5),11(12)-diene synthase; D017239:Paclitaxel