© Benaki Phytopathological Institute
Endophytic fungi & secondary metabolites in medicinal plants
59
ply because each lineage has benefitted
from making a given compound completely
independently of the other or whether hori-
zontal gene transfer (HGT) events took place
between the fungi and the plant.
There is precedent for the indepen-
dent development of the same biosynthet-
ic pathway (biochemical convergence) in
fungi or plants and other organisms. For in-
stance, although higher plants and endo-
phytic fungi produce structurally identical
GAs, profound differences have been found
in the GA pathways and enzymes of plants
and fungi (Hamayum
et al
., 2016), e.g. 7-m-
ethyl-cyercene-1 found in both the fungus
Leptosphaeria maculans
(anamorph
Pho-
ma lingam
) and the marine mollusk
Ercol-
ania funereal
is produced by distinct en-
zymes (Cutignano
et al
., 2012). Cyanogenic
glucosides linamarin and lotaustralin found
in both the moth
Zygaena filipendulae
and
their food plant
Lotus japonicus
are biosyn-
thesized by distinct enzyme systems(Jensen
et al
., 2010). However, a horizontal gene
transfer event between plants and fungi, al-
though rare, should not be excluded (Rich-
ards
et al
., 2009).
Several studies have reported the pres-
ence of
Taxus
tree key genes (
ts
,
dbat
and
bapt
) which are involved in plant paclitaxel
biosynthesis in taxol-producing endophytic
fungi. These results stimulated the conjec-
ture that the origin of this pathway in these
two physically associated groups could have
been facilitated by horizontal gene transfer
(Kusari
et al
., 2014). Other studies, howev-
er, provided evidence that microbial taxol
genes exist independent of the plant genes
(Xiong
et al
., 2013). Recent data support the
latter proposal; genome sequencing and
analysis of the taxol-producing endophyt-
ic fungus
Penicillium aurantiogriseum
NRRL
62431 revealed that out of 13 known plant
Taxol biosynthetic genes, only 7 showed low
homology(>30%) with genes identified in
P.
aurantiogriseum
(Yang
et al
., 2014)
.
Further-
more, polyclonal antibodies against Yaxus
TS strongly cross-reacted with a protein of
the taxol-producing fungus
Paraconiothyri-
um
SSM001 grown in liquid culture, where-
as PCR analysis did not reveal the presence
of
Taxus
ts
gene sequences in SSM001 (Soli-
man
et al.
, 2013). Hence, the divergence of
the two biosynthetic pathways is support-
ed with conservation only in specific en-
zyme sites to be important for the activi-
ty rather than the whole protein structure.
Similar findings have been reported in the
case of huperzine A producing endophytes.
Their fungal amine oxidase genes have
been found to present low similarities to the
corresponding plant genes, and only con-
served consensus sequences were present
by the fungal and plant functional amine
oxidase proteins (Yang
et al
., 2014; Yang
et
al
., 2016; Zhang et al.,
2015
), which supports
the co-evolution theory rather than the HGT
theory. This has been well established in the
case of gibberellin biosynthetic pathways in
fungi and higher plants where differences
in genes and enzymes indicated converged
evolution of GA metabolic pathways (Böm-
ke and Tudzynski, 2009).
The list of taxol producing endophyt-
ic fungi is large and encompasses numer-
ous fungi belonging to diverse genera (Sti-
erle and Stierle, 2015). A similar situation
appears to hold for CPT-producing fungi (Pu
et al
., 2013) and HupA-producing endophytic
fungi (Su
et al
., 2017) suggesting a horizontal
transfer of large secondary metabolism gene
clusters between fungi. Several studies offer
support to this idea; the complete sterigma-
tocystin
gene cluster in
Podospora anserine
was horizontally transferred from
Aspergil-
lus
(Slot and Rokas, 2012). Furthermore, it has
been shown that CTP is also produced by a
diverse group of endophytic bacteria (Shwe-
ta
et al
., 2013; Pu
et al
., 2015) suggesting that
bacterial CPT biosynthesis may represent
an independently assembled pathway from
that in fungi or plants. This may be surpris-
ing since converged evolution of the diter-
pene GA metabolic pathway in plants, fungi
and bacteria is well established (Tudzyns-
ki
et
al
., 2016). Therefore, extensive genome
sequencing of the various endophytic fun-
gi will provide an opportunity for a compre-
hensive study on the phylogenetic origin of
fungal and bacterial metabolic pathways.
