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SEQUESTRATION, RELEASE AND ECOLOGY OF THE ANTICANCER DRUG TAXOL FROM FUNGAL ENDOPHYTES

Sameh S.M. Soliman , John Greenwood, Aureliano Bombarely, Lukas A. Mueller, Rong Tsao, Dick Mosser and Manish N. Raizada

Department of Pharmacognosy and Medicinal Chemistry, School of Pharmacy, University of Sharjah, UAE

Abstract

Taxol, the most known anticancer drug is produced by Taxus trees and their resident endophytic fungi. A mystery has been why both the tree and its resident non-pathogenic fungi (endophytes) biosynthesize Taxol, apparently redundant. A defining feature of these trees is that they can propagate branches from long-lived buds that lie underneath the bark; resulting in persistent bark cracking and deep air pockets, potentially allowing pathogens to enter the nutrient-rich vascular system (vertical phloem and interconnected radial medullary rays [MR]). These endophytes, as well as pure Taxol, suppress fungal pathogens including wood-decaying fungi (WDF). Taxol-producing fungal endophyte, Paraconiothyrium SSM001, migrates to pathogen entry points including branch cracks. The fungus sequesters Taxol in intracellular hydrophobic bodies that are induced by WDF for release by exocytosis, after which the bodies can coalesce to form remarkable extracellular barriers, laced with the fungicide. We propose that microbial construction of fungicide-releasing hydrophobic barriers might be a novel plant defense mechanism. We further propose that the endophyte might be evolutionarily analogous to animal immune cells, in that it might expand plant immunity by acting as an autonomous, anti-pathogen sentinel that monitors the vascular system.