9.8 Current Challenges
To achieve a competent endophyte with promising bioactivity is a challenging task
(Scherlach and Hertweck 2009 ; Kusari et al. 2012 ). In the traditional way, this
requires screening of a plethora of endophytes from a host. Most of the isolating
endophytes are incompetent, i.e., they do not possess desired potential to produce
bioactivity. However, whole-genome sequencing strategies have revealed that the
incompetent endophytes express only a subset of biosynthetic genes under labo-
ratory culture conditions (Scherlach and Hertweck 2009 ; Winter et al. 2011 ).
Therefore there is possibility of utilizing the large reservoir of cryptic natural
metabolites by experimenting with different in vitro culture conditions and under-
standing the chemical ecological interactions of endophytes (Kusari et al. 2012 ).
Another major challenge is the low yield of the active desirable compound/s
obtained from the cultures (Yu et al. 2010 ; Aly et al. 2011 ). This is a major
drawback for bioactive compounds from entering the commercial industry. For an
example, the yield of the anticancer drug paclitaxel obtained from several endo-
phytic fungal cultures are 846.1, 187.6 and 163.4μgL−^1 , which is too low for
commercial production (Gangadevi and Muthumary 2008 ; Liu et al. 2009 ).
Therefore, so far fungal endophytes have not been an industrial source of paclitaxel
(Aly et al. 2011 ) or any other pharmaceutical. However, genetic engineering
technology and research identifying the regulatory gene/s in the biosynthesis
pathway of the active compound can lead to increase production of the compounds
(Yu et al. 2010 ; Radic and Strukelj 2012 ).
The mammalian toxicity of any prospective drug developed has also become a
major concern in thefield (Yu et al. 2010 ). Most of these isolated bioactive
metabolites precluded clinical use due to the toxicities to animals and humans
(Waring and Beaver 1996 ). However, Strobel ( 2003 ) stated that plants as an
eukaryotic system, have naturally served as a selection system for microbes having
bioactive molecules with reduced toxicity toward higher organisms.
Compounds showing moderate biological activity most often cannot be used as
potential chemotherapeutic agents (Yu et al. 2010 ). Totally or partly unknown
biosynthesis, regulation, and synthesis, of these natural products in endophytes are
other issues in thefield (Yu et al. 2010 ). The rapidly diminishing rainforests, which
is a huge reservoir for novel fungal endophytes and their bioactive products, is one
of the major problems facing the future in this area (Strobel 2003 ). Therefore,
countries need to establish information repositories of their biodiversity and at the
same time should take conservation measures to protect the biodiversity.
Despite speculation by many authors no endophytic fungal-derived metabolite
has so far become commercially useful (Kusari and Spiteller 2011 ). However,
interest in the biosynthetic abilities of the endophytic fungi by the scientific com-
munity has not diminished but in fact is on the rise.
9 Endophytic Fungi: A Remarkable Source... 207