Several earlier reports showed that Taxol levels in suspension cultures  and intact trees [23, 24] vary by up to 125-fold, but the underlying reason has never been shown. Independent studies showed that Taxol-producing fungal endophytes elicit the production of Taxol from in vitro Taxus cell cultures , though did not determine the mechanism of elicitation. Here we present data that these two phenomena are mechanistically related. Specifically, we have shown that tree-to-tree, and even branch-to-branch, variation in Taxus plant Taxol accumulation positively correlates with the quantity of a resident Taxol producing fungal endophyte, in this case Paraconiothyrium SSM001 (Figure 1, 2). The underlying mechanism involves endophyte-induced transcriptional activation of rate limiting genes in the plant Taxol biosynthetic pathway (Figure 3).
Given that the natural environment of the endophytic fungal strain is Taxus wood, and that Taxol was reported to be a fungicide , we hypothesized that the endophyte might stimulate its host to produce Taxol in order to inhibit fungal competitors that could also colonize the same woody environment. Consistent with this hypothesis, Taxol inhibited growth of fungi known to infect conifer wood including Taxus wood (Figure 4).
Nevertheless, this raises an important question as to why the endophyte needs to stimulate the host plant to produce Taxol when the endophtye can produce the same secondary metabolite by itself, at least in vitro. We propose that this endophyte strategy may be to prevent colonization by its competitors but at minimal metabolic cost to itself. We have recently shown that Taxol biosynthesis in this fungal endophyte (Paraconiothyrium SSM001) consumes expensive terpenoid and phenylpropanoid pathway metabolites . Such a relationship between Taxus and its fungal endophyte, wherein the endophyte takes advantage of its host, would represent an interesting example of commensalism.
These results raise the reverse question: why does the Taxus host retain an endophyte that produces a secondary metabolite that it can synthesize on its own? Our results even demonstrate that an antibody raised to recognize taxadiene synthase (TS), the rate limiting step in plant Taxol biosynthesis, strongly cross reacts to the apparent endophyte TS (Figure 3G), a result which appeared to be confirmed using a negative control (non-Taxol producing Fusarium fungus) and positive controls (two fungal Taxol elicitors) (Additional file 6). This result suggests a shared evolutionary relationship between plant and fungal endophyte Taxol biosynthetic pathways, rather than convergent evolution. One attractive possibility is that if a pathogen were able to successfully colonize the host, the plant may not be able to produce Taxol locally due to the resulting plant tissue damage. By the host maintaining a Taxol-producing endophyte, even at a metabolic cost to itself in the short-term, it may afford itself long-term protection against systemic infection in situations where it can no longer produce the Taxol fungicide – a temporal form of symbiosis. Testing this hypothesis would require being able to chemically trace the biosynthetic origin of Taxol in planta before and after a fungal pathogen infection.
Other fungi have also been shown to elicit plants to produce terpenoid-based compounds in planta[30–32]. Arbuscular mycorrhizal fungi induce the accumulation of mycorradicin in gramineous plant roots by inducing 1-deoxy-D-xylulose 5-phosphate synthase (DXS) and DXR, two key enzymes in the MEP pathway [30, 31]. Terpenoid production in Euphorbia pekinensis (Rupr) plants increases upon inoculation with the endophytic fungus, Phomopsis sp., by induction of plant phenylalanine ammonia-lyase (PAL) and DXR. Finally, fungal elicitors have been shown to induce biosynthesis of the anti-malarial terpenoid, artemisinin, in Artemisia annua (L.) plant suspension cells .
On a cautionary note, as only a modest correlation was observed between SSM001 and plant Taxol concentrations, and since the fungicide treatments did not specifically target SSM001, it is possible that other fungi within Taxus might also elicit plant Taxol biosynthesis, consistent with Taxol acting as a fungicide. Recently, we also demonstrated that other fungi inhabiting Taxus can elicit Taxol production from the endophytic fungus in vitro, raising the possibility of complex elicitor interactions on Taxol accumulation in planta.