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Medicinal Plants – Chemical, Biochemical, and Pharmacological Approaches
41
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Secondary metabolite Host plant Endophyte Strain Ref
Lycopodium
serratum
H. serrata Shiraia sp. Fungal [155]
Phlegmariurus
phlegmaria
H. serrata Colletotrichum sp., Ascomycota sp.,
Phlegmariurus
taxifolius
H. serrata Fusarium sp. Fungal [170]
CPT and active derivative 10-hydroxyCPT, podophyllotoxin, deoxypodophyllotoxin act as anticancer, and Huperzine A
approved for treatment of Alzheimer’s disease.
Penicillium chrysogenum Fungal [154]
Cladosporium cladosporioides Fungal [156]
Aspergillus flavus Fungal [157]
Shiraia bambusicola Fungal [158]
Colletotrichum gloeosporioides Fungal [159]
Trichoderma sp. Fungal [160]
Paecilomyces tenuis Fungal [161]
Penicillium sp. Fungal [162]
Ceriporia lacerate Fungal [163]
Sarcosomataceae sp., Dothideomycetes sp.
Penicillium sp. Fungal [165]
Alternaria brassicae Fungal [166]
Penicillium polonicum, Colletotrichum
gloeosporioides
Mucor racemosus, M. fragilis, Fusarium
verticillioides, F. oxysporum,Trichoderma
harzianum
Fusarium sp. Fungal [169]
Fungal [164]
Fungal [167]
Fungal [168]
Table 3.
Production of plant-derived secondary metabolites by endophytic microorganisms.
3.4 Podophyllotoxin
Podophyllotoxin is an aryltetralin lignin that uses in the synthesis of anticancer
drugs. It is originally isolated from the resins of the Podophyllum emodi, which is
traditionally used to treat genital warts [16]. Podophyllotoxin is a strong inhibitor of
microtubules, while its derivatives inhibit topoisomerase 2. These derivatives are used
to treat bronchial and testicular cancers. Podophyllotoxin production from endophytic
fungi isolated from Podophyllum [syn. Sinopodophyllum] hexandrum, Diphylleia
sinensis, and Dysosma veitchii were reported for the first time [134]. After that, two
strains of the endophytic fungus Phialocephala fortinii from the rhizome of
P. peltatum, which could produce podophyllotoxin under axenic culture conditions,
were isolated and identified [138]. The fungus Trametes isolated from P. hexandrum is
another endophyte capable of producing podophyllotoxin and podophyllotoxin glycosides [139]. In addition, F. oxysporum and Aspergillus endophytes isolated from
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Endophytes: A New Resource for Vulnerable Plant Bioactive Compounds
ITexLi.112931
Juniperus
phyllotoxin,
reported
found
fungi
and
podophyllotoxin-producing
ium
among
Fungal production of podophyllotoxin is promising for mass production, and it is
possible
cultivation
reducing
producing
3.5
recurva and Juniperus communis produced podophyllotoxin and deoxypado-
respectively [141, 151]. Podophyllotoxin production has also been
from Mucor fragilis, and Alternaria tenuissima isolated from P. emodi was
to
produce podophyllotoxin [143, 144]. Podophyllotoxin-producing endophytic
Penicillium sp., Trametes sp., Purpureocillium sp., Aspergillus sp. Ganoderma sp.,
Fusarium spp. were isolated from plants of Dysosma spp. [149, 150].
fungi belong to Penicillium sp., Alternaria sp., and Fusar-
spp. genera, respectively, While there is no report of podophyllotoxin production
endophyte bacteria (Table 3).
to
provide affordable resources for commercial production by optimizing the
methods and genetic changes of the producing microorganisms and
the pressure of harvesting from plant resources and giving the chance to
plants for save from extinction.
Huperzine A
Most
The lycopod
called
Huperzine A (HupA), which has attracted worldwide attention for its potential
the treatment of Alzheimer’s disease. This compound is an acetylcholinesterase
in
inhibitor
by
highly selective and reversible inhibition of this enzyme and blocking its activity.
bulk of HupA is obtained from the Huperziaceae family. The H. serrata has a
The
narrow
which
phyte
HupA
cladosporioides isolated from H. serrata leaves also produced HupA [155, 156, 158].
general,
These
ing
Xia and colleagues isolated endophytic fungi
verticillioides,
can
cessfully
acetylcholinesterase
phytes,
tion
strategy
genetic
geographical distribution, slow growth rate, and very low HupA content,
limits its natural harvest and HupA extraction. In the first report, the endo-
Acremonium sp. isolated from H. serrata has been capable of production
[152]. Similarly, the endophyte Shiraia sp. Slf14 and Cladosporium
32
fungal endophytes were isolated from members of Huperziaceae family, includ-
H. serrata, Phlegmariurus phlegmaria, and Phlegmariurus taxifolius (Table 3) [171].
inhibit acetylcholinesterase enzyme [168]. The endophyte Ceriporia lacerate suc-
transformed HupA into five different compounds that showed potential
is
of
HupA has positive economic and environmental effects. This will be a practical
to
manipulation of the source fungi.
Huperzia serrata is the main source of a natural lycopodium
that increases the availability of acetylcholine in central cholinergic synapses
alkaloid
of
endophytic fungi belonging to 15 genera were recorded to produce Hup A.
Mucor racemosus, M. fragilis, Fusarium
F. oxysporum, and Trichoderma harzianum from the H. serrata, which
inhibitory activity [172]. Biotransformation, using fungal endo-
also a valuable approach to producing HupA derivatives. Microbial produc-
meet the global market demand through microbial fermentation and
In
4. Industrial
The role of plant compounds in the production of many clinically effective anti-
cancer
expected.
many
certain
of
11
drugs is undeniable, but the production of herbal drugs is not always as
of
environmental conditions, stress, or availability of nutrients. Also, the growth
plants is slow, and to collect and extract some products, they must reach acceptable
aspects
Because their production from plant resources faces serious challenges,
these compounds are produced at a certain stage of plant growth or under
Medicinal Plants – Chemical, Biochemical, and Pharmacological Approaches
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growth. On the other hand, production in plant cell culture also faces technical challenges. Also, due to the extent and variety of bioactive in plants, the purification
processes of the desired effective substances will be complicated and therefore
expensive. Due to the limitations identified with the productivity and vulnerability of
plant species as sources of new metabolites, microorganisms act as an available and
inexhaustible resource of new pharmaceuticals [173].
Over many years, seasonal and climatic factors have caused failure in
traditional methods of extracting bioactive from natural resources. The environmental
issues that researchers face during the extraction of bioactive from plants make it
necessary to adopt new approaches to obtain these compounds [174]. In the future,
with the increase in population, the demand for pharmaceutical and agricultural
products will increase day by day, and the future of endophytic fungi for the
isolation of various beneficial compounds is bright. There is a great need to discover
bioactive compounds from natural resources that can be used to treat various diseases.
Recently, more attention has been paid to the production of bioactive from endophytic fungi because they are excellent for exploiting the biosynthetic pathway for the
synthesis of bioactive. The main challenge is the low yield of desired active compounds obtained from endophytes. However, to meet the demand of pharmaceutical
companies to increase the commercial production of drugs, genetic engineering technologies, drug design techniques, and microbial fermentation technology can be solutions to increase the rate of endophyte production [2]. In addition, the use of cell cocultures of host plants and endophytes has improved the production rate. Some
secondary metabolites may be produced by combined endophyte and host activity.
Some endophytic bacteria produce secondary metabolites in medicinal plants. For
example, Bacillus altitudinis, Burkholderia sp., and Flavobacterium sp. act as
effective stimulators that increase ginsenoside concentrations by converting the
major ginsenoside Rb1 to the minor ginsenoside Rg3 in the valuable medicinal plant
ginseng [175–177]. Such biotransformations using endophytic bacteria have
significant potential to intensify the accumulation of rare active substances in
medicinal plants. The endophytic Pseudomonas fluorescens can increase the
production of sesquiterpenoids in Macrocephala Atractylodes [178]. The endophyte
Bacillus subtilis in the plant Chuanxiong Ligusticum enhances ligustrazine
accumulation [179].
The interaction of endophytes with plant tissues asymptomatically increases the
production of secondary metabolites. A double synthesis of podophyllotoxin was
obtained from the interaction of endophytic fungi Phialocephala fortinii and rhizomes
of P. peltatum [138]. Endophytic fungi Stemphylium amaranthi and Gliomastix
masseei can be used as fungal stimulants to improve indole alkaloid production from
C. roseus [180].
5. Conclusion
Throughout history, humans have used plants and plant-derived products to treat
various ailments. Plant secondary metabolites or bioactive are known to be synthesized by plants. Microbes living inside host plant tissues are also known for their
ability to synthesize substances similar to those synthesized by the host plant. Secondary metabolites, such as alkaloids, flavonoids, terpenoids, steroids, etc. synthesized by microbes, are known for their vital role as antioxidants and anticancer. The
discovery of the ability to produce plant secondary metabolites in endophytes has
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Endophytes: A New Resource for Vulnerable Plant Bioactive Compounds
ITexLi.112931
many hopes for the production of these compounds on an industrial scale.
raised
Microorganisms
substances
possibility of their genetic manipulation is easier, and the fermentation conditions
the
them are simpler, cheaper, and more diverse.
for
reduce environmental concerns about the production of biological
in
plants because endophytic microbes have a high reproduction ability,
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