In this article the authors discusses the use of endophytic fungi as substitute of plant secondary metabolites. It states that endophytic fungi exist internally in plants and enhance the plants' ability to tolerate abiotic and biotic stresses. Endophytic fungi if cultured outside their host can produce secondary metabolites such as anti-cancer, anti-fungal, anti-diabetic and immunosuppressant compounds

Ganeshaiah, KN

Priti, V

Ramesha, BT

Ravikanth, G

Singh, Shweta

Suryanarayanan , TS

Uma Shaanker, R

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OPINION 
 
CURRENT SCIENCE, VOL. 97, NO. 4, 25 AUGUST 2009 477
How promising are endophytic fungi as alternative sources of  
plant secondary metabolites? 
 
V. Priti, B. T. Ramesha, Shweta Singh, G. Ravikanth, K. N. Ganeshaiah, T. S. Suryanarayanan and  
R. Uma Shaanker 
 
Endophytic fungi, which colonize plants 
internally without apparent adverse effects, 
occur ubiquitously in plants1. In contrast 
to their pathogenic fungal counterparts, 
the endophytic fungi exist in a mutualis-
tic association with their host plants, and 
in few cases, enhance the ability of 
plants to tolerate abiotic2 and biotic3 
stresses. In culture, outside of their host 
tissue, endophytic fungi are also known 
to produce a number of important secon-
dary metabolites including anti-cancer, 
anti-fungal, anti-diabetic and immuno-
suppressant compounds1,4. Occasionally, 
these compounds are the same as those 
produced by the respective host plants, 
thus triggering the expectation that 
endophytic fungi can serve as an alterna-
tive source of important plant secondary 
metabolites. This possibility was perhaps 
first realized and mooted by Stierle and 
his co-workers, following their discovery 
that the endophytic fungus Taxomyces 
andreanae of the yew plant Taxus brevi-
folia could also produce taxol (generic 
name: paclitaxel), the multi-billion dollar 
anti-cancer compound produced by the 
yew plant5. Since the discovery of taxol 
from Taxus brevifolia6, the world’s sup-
ply of taxol comes from these trees. 
However, because of the destructive fell-
ing of trees for their bark coupled with 
their slow growth, the existing natural 
stocks of trees is fast depleting, and it is 
feared that it would not sustain the global 
demand. In this context, the discovery of 
Stierle and his co-workers5 was heralded 
as very significant and it raised the hope 
of using the endophytic fungus as a sus-
tainable alternative source of taxol. But, 
how far has this hope been realized? 
Here, we critically address this question.  
 Spurred by Stierle et al.5 discovery, 
scores of studies have been made to iden-
tify endophytic fungal sources of a number 
of important plant secondary metabolites 
as revealed by Strobel and Daisy7. In 
fact, since the publication of the report 
by Stierle and his co-workers5, there has 
been a monotonic increase in the number 
of US patents filed on endophytic fungi 
producing important metabolites with  
diverse biological activities (Figure 1).  
 It would be illustrative to narrate a few 
studies, especially those that have been 
prospected for anti-cancer compounds. 
For example, besides Taxomyces andre-
anae, a number of other endophytic fungi 
including Seimatoantlerium tepuiense 
and S. nepalense have been reported to 
produce paclitaxel8. Another anti-cancer 
agent, a selective cytotoxic quinine dimer, 
torreyanic acid was isolated from the 
endophyte Pestalotiopsis microspora  
associated with the endangered tree Tor-
reya taxifolia (Florida torreya)9. Torrey-
anic acid is 5–10 times more potent than 
taxol, and causes cell death by apopto-
sis9. Three novel cytochalasins including 
22-oxa-(12)-cytochalasins with anti-
tumour activity were reported from Rhi-
nocladiella sp., an endophye of Triptery-
gium wilfordii10. Extracts of Curvularia 
sp., an endophytic fungus isolated from 
Ocotea corymbosa, yielded two new ben-
zopyran derivatives and two known 
compounds that were tested in cell pro-
liferation and anti-fungal assays. Com-
pound (2′S)-2-(propan-2′-ol)-5-hydroxy-
benzopyran-4-1 induced a potent anti-
proliferative stimulus in two mammalian 
cell lines11. Aspergillus niger IFB-E003, 
an endophyte from Cynodon dactylon, 
was found to produce rubrofusarin B 
which is cytotoxic to the colon cancer 
cell line12 SW1116. Entrophospora infre-
quens associated with Nothapodytes 
foetida, a medicinal plant native to the 
Western Ghats, India, was found to pro-
duce camptothecin13. In summary, many 
of these efforts have led to the discovery 
of endophytic fungi as a source of a 
number of important metabolites and 
have raised the prospect of using such 
organisms as alternative sources of these 
metabolites. 
 Notwithstanding these discoveries, 
however, to date there has been no known 
published breakthrough in exploiting the 
potential of the endophytic fungi as a 
source of important secondary metabo-
lites. None of the identified endophytic 
fungal isolates has had any industrial  
application as yet. In 2002, Strobel who 
started it all said, ‘efforts are underway 
by several pharmaceutical companies to 
determine the feasibility of making  
microbial taxol a commercial reality’14. 
Seven years later, we have no confirma-
tion of taxol being commercially pro-
duced from its endophytic fungal source. 
In India, taxol continues to be extracted 
from the bark of the rapidly dwindling 
 
 
Figure 1. Cumulative number of US patents granted on endophytic fungi producing
important metabolites and exhibiting biologically important activity (data compiled from 
www.patentsonline.com and www.patentstorm.us). 
OPINION 
 
CURRENT SCIENCE, VOL. 97, NO. 4, 25 AUGUST 2009 478 
natural stocks of Taxus from the Himala-
yan belt region. The picture is the same 
for other compounds produced by endo-
phytic fungi. For example, in yet another 
discovery, Strobel’s team15 claimed that 
an endophytic fungus, Muscudor albus, 
producing volatile organic compounds 
(VOCs) could have significant commer-
cial use in numerous agricultural applica-
tions15. However, these are yet to be 
demonstrated as commercial successes. 
 We believe that the failure of exploiting 
the endophytic fungi rests on our current 
poor understanding of the evolutionary 
significance of these organisms and their 
dynamic interaction with their respective 
hosts (for example, Bailey et al.16). The 
mechanism or process underlying the 
production of the plant secondary meta-
bolites by the endophytic fungi remains 
enigmatic. Even today it is believed and 
not proven that the reason why some 
endophytes produce certain phytochemi-
cals, originally characteristic of the host, 
might be due to a genetic recombination 
of the endophyte with the host in evolu-
tionary time17. In fact, there is less evi-
dence for the horizontal transfer of genes 
coding for secondary metabolites be-
tween plant and fungi18. Furthermore, 
very little is known about the biochemis-
try and physiology of the interactions of 
an endophyte with its host plant. It would 
seem that many factors changing in the 
host as related to the season, age, envi-
ronment and location may influence the 
biology and metabolism of the endo-
phytes (for example, Moricca and Ra-
gazzi19). It is pertinent to mention that 
secondary metabolite production in many 
fungi is regulated by environmental fac-
tors20. Thus not surprisingly, though a 
number of studies have shown the pro-
duction of a specific metabolite by endo-
phytic fungi in culture independent of the 
host, most often the production of bio-
molecules by a nascent endophyte isolate 
is severely attenuated through sub-
culturing21. Consequently, most of the 
endophytic fungi do not lend themselves 
for up-scaling the production through 
fermentation engineering approaches. Al-
though the reasons for such attenuation 
are not extensively studied, it is conjec-
tured that it could be due to a lack of 
host stimulus in the culture media; con-
tinuous and some critical signaling from 
the host may be required by the endo-
phytic fungi to sustain the production of 
such metabolites22. Recent gene sequenc-
ing exercise has shown that the secon-
dary metabolism of fungi in general has 
been little understood and that gene clus-
ters of many secondary metabolites in 
fungi are not expressed in culture23. 
Though a few studies have looked at the 
possibility of horizontal gene transfers 
between the host and endophytic fun-
gus24, it is far from clear how the differ-
ent regulations are imposed. In the few 
elicitation studies conducted so far, there 
is very meagre success, and none of 
these has lead to the recovery of eco-
nomically feasible levels of yield of bio-
active compounds.  
 Despite the highly heralded report of 
endophytic fungi producing taxol in 1993 
and the scores of studies that followed it, 
little progress has been made in harness-
ing the metabolic potential of endophytic 
fungi. Clearly, as mentioned above, more 
research is required to understand the  
biology of these fungi and their intricate 
relationship with their hosts to unravel 
their metabolic pathways and thereby to 
realise their potential utility.  
 
 
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ACKNOWLEDGEMENT. We acknowledge 
financial support from the Department of Bio-
technology, New Delhi. 
 
 
V. Priti, Shweta Singh and K. N. Gane-
shaiah are in School of Ecology and 
Conservation, University of Agricultural 
Sciences, GKVK, Bangalore 560 065,  
India; K. N. Ganeshaiah is also in De-
partment of Forestry and Environmental 
Sciences, GKVK, Bangalore 560 065,  
India; B. T. Ramesha and R. Uma 
Shaanker* are in the Department of 
Crop Physiology and School of Ecology 
and Conservation, University of Agricul-
tural Sciences, GKVK, Bangalore 560 065, 
India; G. Ravikanth is associated with 
Ashoka Trust for Research in Ecology 
and the Environment, Hebbal, Bangalore 
560 024, India; T. S. Suryanarayanan is 
in the Vivekananda Institute of Tropical 
Mycology, RKM Vidyapith, Chennai 
600 004, India. 
*e-mail: umashaanker@gmail.com 
 
 
 


How promising are endophytic fungi as alternative sources of plant secondary metabolites?

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How promising are endophytic fungi as alternative sources of plant secondary metabolites?

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