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Highlights on the Wood Blue-Leg Mushroom Clitocybe Nuda and Blue-Milk Mushroom Lactarius Indigo Ecology and Biological Activities

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The need to improve the life quality together with the increase in the frequency of treating diseases attracted the attention of many researches to view food as a source of nutritional and therapeutical agents. Since earliest times, several mushrooms have been reported as a nutritious food with valuable medicinal properties. The genus Clitocybe and Lactarius belonging to Basidiomycota fungi, is a potential group of edible mushrooms that are distributed in Europe, North America, Asia, Australia and Mexico. The studies on Clitocybe nuda and Lactarius indigo species have revealed high nutritional and medicinal potentials. This review aims to present Clitocybe and Lactarius genus importance as both food and medicine, and which will offer a new vision to researchers to develop new drugs from natural sources.
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Highlights on the Wood Blue-Leg Mushroom Clitocybe Nuda and Blue-Milk Mushroom Lactarius
Indigo Ecology and Biological Activities
Pharm Res
Highlights on the Wood Blue-Leg Mushroom Clitocybe Nuda and
Blue-Milk Mushroom Lactarius Indigo Ecology and Biological
Activities
Elkhateeb WA* and Daba GM
Chemistry of Natural and Microbial Products Department, Pharmaceutical Industries
Researches Division, National Research Centre, Egypt
*Corresponding author: Waill A Elkhateeb, Chemistry of Natural and Microbial Products
Department, Pharmaceutical Industries Researches Division, National Research Centre, El
Buhouth St., Dokki, 12311, Giza, Egypt, Email: waillahmed@yahoo.com
Review Article
Volume 5 Issue 3
Received Date: August 09, 2021
Published Date: September 06, 2021
DOI: 10.23880/oajpr-16000249
Abstract
The need to improve the life quality together with the increase in the frequency of treating diseases attracted the attention
of many researches to view food as a source of nutritional and therapeutical agents. Since earliest times, several mushrooms
have been reported as a nutritious food with valuable medicinal properties. The genus Clitocybe and Lactarius belonging to
Basidiomycota fungi, is a potential group of edible mushrooms that are distributed in Europe, North America, Asia, Australia
and Mexico. The studies on Clitocybe nuda and Lactarius indigo species have revealed high nutritional and medicinal potentials.
This review aims to present Clitocybe and Lactarius genus importance as both food and medicine, and which will offer a new
vision to researchers to develop new drugs from natural sources.
Keywords: Medicinal Mushrooms; Clitocybe nuda; Lactarius Indigo; Biological Activities
Introduction
Mushrooms (Phylum Basidiomycota and Ascomycota)
naturally produce numerous substances with
bioactive properties such as antitumoral, antidiabetic,
immunomodulatory, antioxidant, trypanocide,

[1-10]. The research on new substances have biological
activities especially as antimicrobial is highly necessary,
due to the emergence of resistant bacterial strains and
new opportunistic species. Mushrooms produce a variety
of bioactive compounds that are known to have a potential
source of biological activities. Natural antioxidants can
protect against free radicals without any side effects. For
millennia, mushrooms have been valued by humankind as an
edible and medical resource. The Basidiomycetes mushrooms
are famous for their use as sources of therapeutic bioactive
compounds, such as Geastrum fimbriatum and Hydnellum
peckii which exhibit promising anticoagulant activity.
Handkea utriformis, Hericium erinaceus, Sparassis crispa,
Agaricus blazei and Ganoderma oregonense have wound-
healing capabilities, Trametes versicolor and Dictyophora
indusiata show promising antioxidant, antimicrobial,
antihyperlipidemia, antitumor and immunity enhancement
effects, Fomes fomentarius and Polyporus squamosus have
     
     
[3,5,10-17].
Many mushroom genera are famous for their promising
therapeutic capabilities and one of the mushrooms attracting
attention is Ganoderma lucidum (Reishi), Lentinus edodes
Open Access Journal of Pharmaceutical Research
2
Elkhateeb WA and Daba GM. Analytical Method Development and Validation of Tramadol
Hydrochloride by Pharmaceutical Dosage Form by Ultraviolet Spectroscopy. Pharm Res 2021, 5(3):
000249.
Copyright© Elkhateeb WA and Daba GM.
(Shiitake), Inonotus obliquus (Chaga) and many others have
been collected and used for hundreds of years in Korea, China,
Japan, and eastern Russia. Those practices still form the basis
       

All these vital activities have been reported from extracts of
fruit bodies of these mushrooms or their biologically active
isolated compounds [18-28]. Polysaccharides are the best
known and most potent mushroom derived substances with
antitumor and immunomodulating properties. Biologically
active polysaccharides are widespread among higher
Basidiomycetes mushrooms, and most of them have unique
structures in different species. Moreover, different strains
of one Basidiomycetes or Ascomycetes species can produce
polysaccharides with different properties [29-39]. This
review describes pharmacologically active compounds from
mushrooms.
Clitocybe Nuda
Clitocybe nuda also known as Lepista nuda, and
sometimes given the common name “blewit or blue-Leg
mushroom. Clitocybe nuda belonging to; Basidiomycota;
Class: Agaricomycetes; Order: Agaricales; Family
Tricholomataceae. Clitocybe nuda is fairly easily recognized
when fresh and young, but older specimens can be confused
with many potential look-alikes. Gorgeous shades of lilac
and lavender on the cap, gills, and stem fade quickly; the cap
becomes brownish, and the gills and stem fade to buff. But
this color transformation is one of the mushroom›s unique
features, along with its pale pinkish spore print, its lack of
a partial veil, and its tendency to grow in plenty on organic
remains. Clitocybe nuda may look innocent enough, from a
human perspective, Clitocybe nuda sends out tiny hyphae
that penetrate bacteria colonies and kill them, sucking up
their nutrients.
Clitocybe nuda ecology: Saprobic; growing alone,
scattered, or in clusters in organic debris in woods or in
urban locations; late summer and fall; widely distributed
in North America. Cap: 4-20 cm; convex with an enrolled

or with an uplifted, wavy margin in age; surface smooth,
       
the center; usually dull purple, or purplish with brown

lighter. Gills: Attached to the stem sometimes by a notch or
beginning to run down it; close or crowded; pale lavender
to lilac, fading to buff, pinkish buff, or brownish. Stem: 3-10
cm long; 1-3 cm thick at apex; equal, or enlarged at the base;
         
or colored like the gills; becoming brownish in age; base
often covered with lilac to buff mycelium. Flesh: Thick; soft;
purplish to lilac-buff or whitish. Odor and Taste: Taste not
distinctive, pleasant, or slightly bitter; odor fragrant. Spore
Print: Pinkish. Microscopic Details: Spores 5.5-8 x 3.5-5
µ; ellipsoid; roughened or sometimes smooth; in amyloid.
Cystidia absent Pileipellis a cutis of hyphae 1-4 µ wide. Clamp
connections present (Figures 1, 2) [40-43].
Figure 1: Clitocybe nuda, (Photo was taken by: Damon
Tighe. Locality: United States, California, Knowland Park,
Oakland (Cited in: https://mycoportal.org).
Figure 2: Clitocybe nuda, (Photo was taken by Evan Casey.
Locality: United States, California, San Bernardino, Yucaipa
(Cited in: https://mycoportal.org).
Clitocybe nuda biological activities
Clitocybe nuda (Fr.) (Lepista nuda, commonly known
as wood blewit or blue stalk mushroom) is an edible
woodland mushroom found in Europe, North America, Asia,
and Australia [44]. Due to its special cologne and delicate
texture, it has been cultivated in France, Holland, Britain, and
Taiwan. Several bioactive extracts from Clitocybe nuda have
been found to exhibit antioxidant and antimicrobial
properties [45]. Furthermore to its edible properties, many
researchers have conducted biological activity studies on
Clitocybe nuda. Many studies have shown that Clitocybe
nuda mushroom has, antimicrobial, cytotoxic, enzymatic,
antiviral and antiproliferative activities [46]. As a result,
Clitocybe nuda, which is an edible mushroom, has important
medicinal properties in addition to its nutritional properties
[47]. Clitocybe nuda is reported to exhibit many biological
Open Access Journal of Pharmaceutical Research
3
Elkhateeb WA and Daba GM. Analytical Method Development and Validation of Tramadol
Hydrochloride by Pharmaceutical Dosage Form by Ultraviolet Spectroscopy. Pharm Res 2021, 5(3):
000249.
Copyright© Elkhateeb WA and Daba GM.
activities. Clitocybe nuda extract was studied its action on
HL60 (leukemia) and MCF7 (breast cancer) cancer cell lines
        

with drugs protocatechuic acid, paclitaxel and doxorubicin
against HL-60 cell line with regard to both proliferation and
apoptotic effects (>%75).
Clitocybe nuda was extracted, with 95% ethanol and
the extract showed good antibacterial activity against four
pathogenic foodborne bacteria: Listeria monocytogenes,
Salmonella typhimurium, Escherichia coli and Staphylococcus
aureus [49,50]. Secondary metabolites of Clitocybe nuda
displayed antimicrobial activity against Phytophthora capsici.
    Clitocybe nuda was extracted with
ethanol and chromatographically separated on a Sephadex
LH-20 column and fractionated on a silica gel column to give
eight fractions. These fractions were tested for the ability to
inhibit zoospore germination of Phytophthora capsici. The

chromatography to yield three compounds: 2-methoxy-
5-methyl-6-methoxymethyl-p-benzoquinone, 6-hydroxy-
2H-pyran-3-carbaldehyde, and indole-3-carbaldehyde.
At a concentration of 500 mg/L, indole-3-carbaldehyde
showed complete inhibition of zoospore germination, while
2-methoxy-5-methyl-6-methoxymethyl-p-benzoquinone
and 6-hydroxy-2H-pyran-3-carbaldehyde, showed inhibition
rates of 97 and 86%, respectively.
    Clitocybe nuda was studied by
Chen and Huang, and reported that Clitocybe nuda culture
       
of Colletotrichum higginsianum   
Clitocybe nuda contained substances that had the capacity
to completely inhibit spore germination of Alternaria
brassicicola. Clitocybe nuda 
suppression of spore germination of Phytophthora capsici
and moderately inhibited spore germination of Fusarium
oxysporum     Clitocybe nuda and
Coprinus comatus effectively reduced the disease severity
of Phytophthora blight of pepper caused by Phytophthora
capsici. All these results suggest that substances from
edible mushrooms have the potential to be developed into
biocontrol agents for the control of plant diseases [51].
Lactarius indigo
Lactarius indigo belonging to; Basidiomycota; Class:
Agaricomycetes; Order: Russulales; Family Russulaceae.
Lactarius indigo it is a truly beautiful, blue species that
exudes dark blue milk when damaged with a knife point.
Only Lactarius indigo, Lactarius chelidonium and Lactarius
paradoxus come close in appearance and they only do so when
very young, before they have begun to develop their brown
and yellow shades (they also have yellowish and brown milk,
respectively). Lactarius indigo description; small cap (3-5
cm across), flesh that turns green within a few minutes of
exposure, and a pure white spore print. Lactarius indigo was
found in many diverse ecosystems from oak-hickory forests
to ponderosa pine zones in the southwestern United States to
cloud forests in Mexico. Ecology: Mycorrhizal with oaks and
with pines; growing alone, scattered, or grouped; summer
and fall; fairly widely distributed in North America from
the northeast to the southwestern United States, Texas, and

         
when fresh; grayish or silvery blue when faded; sometimes
developing brownish areas when old; with concentric zones
of color, or sometimes evenly colored; sticky or slimy when
fresh; bruising and discoloring deep green, especially with
age. Gills: Attached to the stem or beginning to run down
it; close; colored like the cap or a little paler; becoming
nearly yellowish at maturity; staining green. Stem: 2-8 cm
long; 1-2.5 cm thick; equal or tapering to base; sometimes a

usually with potholes on the surface. Flesh: Whitish, turning
indigo blue when cut; staining slowly greenish. Milk: Deep
indigo blue; becoming dark green on exposure. Odor and
Taste: Odor not distinctive; taste mild to (sometimes) slowly,
slightly acrid. Spore Print: Cream. Microscopic Features:
Spores 7-10 x 5.5-7.5 µ; broadly ellipsoid to subglobose;
ornamentation about 0.5 µ high, as amyloid warts and
connecting lines that sometimes form partial reticula.
Pleuromacrocystidia cylindric-ventricose; inconspicuous;
to about 60 x 8 µ. Cheilocystidia inconspicuous; clavate to
subcylindric; to about 30 x 6 µ. Pileipellis an ixocutis (Figures
3, 4) [54, 55].
Figure 3: Lactarius indigo, (Photo was taken by: Patricia R.
Miller. Locality: USA, Mississippi, Grenada, Grenada Dam,
(Cited in: https://mycoportal.org).
Open Access Journal of Pharmaceutical Research
4
Elkhateeb WA and Daba GM. Analytical Method Development and Validation of Tramadol
Hydrochloride by Pharmaceutical Dosage Form by Ultraviolet Spectroscopy. Pharm Res 2021, 5(3):
000249.
Copyright© Elkhateeb WA and Daba GM.
Figure 4: Lactarius indigo, (Photo was taken by Patricia
R. Miller. Locality: USA, Mississippi, Lafayette, Oxford,
Washington Ave. (Cited in: https://mycoportal.org).
Lactarius indigo biological activities
The major role of Lactarius indigo in the world is in
cooking. It is known for its fascinating color and the cultural
significance it has in countries such as Mexico [56]. However,
research has indicated the mushroom has antibacterial
and cytotoxic properties [57]. Bioassays and cytotoxic
assays were created to compare the inhibition of strains
with only hexane and methanol versus with the Lactarius
indigo. When tested against different bacteria, such as
diarrheagenic Escherichia coli strains, the Lactarius indigo
inhibited proliferation of certain pathogenic bacteria, the
inhibitory effect depended on the bacteria it was tested
against and the dosage of Lactarius indigo. Overall, the study
indicated possible medicinal properties in L. indigo [57]. Both
aqueous and organic extracts of Lactarius indigo basidiocarp
have pharmacological activity, Ochoa-Zarzosa, et al., show
that the basidiocarp of the edible Lactarius indigo is a source
of pharmacological substances having varied therapeutic
applications, which makes it necessary to perform further
studies in that regard by isolating and characterizing the
molecules responsible for the observed activities [58].
Conclusion
Basidiomycetous mushrooms represented by Clitocybe
nuda and Lactarius indigo have a rich history of use as a food
source and well-claimed medicinal properties. This review
summarises a number of sources with details of nutritional

to antitumor, health-promoting nutrients and others). Despite
these advances, there is much we have yet to understand and
these hypogeal fruiting Basidiomycetes prove to be a fruitful
source of novel medicinal compounds.
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Cordyceps; Current knowledge and prospective
potentials. Biofarmasi Journal of Natural Product
Biochemistry 18(2): 70-77.
4. Elkhateeb WA, Daba GM (2020) Termitomyces Marvel
Medicinal Mushroom Having a Unique Life Cycle. Open
Access Journal of Pharmaceutical Research 4(1): 1-4.
5. Daba GM, Elkhateeb W, EL Dien AN, Fadl E, Elhagrasi A,
et al. (2020) Therapeutic potentials of n-hexane extracts
of the three medicinal mushrooms regarding their anti-
colon cancer, antioxidant, and hypocholesterolemic
capabilities. Biodiversitas Journal of Biological Diversity
21(6): 1-10.
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do?. Chem Res J 5(1): 106-118.
7. Elkhateeb WA, Daba GM, Elmahdy EM, Thomas PW,
Wen TC, et al. (2019) Antiviral potential of mushrooms
in the light of their biological active compounds. ARC J
Pharmac Sci 5(2): 45-49.
8. El-Hagrassi A (2020) In vitro bioactive potential and
chemical analysis of the n-hexane extract of the medicinal
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9. Elkhateeb WA, Daba GM, El-Dein AN, Sheir DH, Fayad W, et
al. (2020) Insights into the in-vitro hypocholesterolemic,
antioxidant, antirotavirus, and anticolon cancer
activities of the methanolic extracts of a Japanese lichen,
Candelariella vitellina, and a Japanese mushroom,
Ganoderma applanatum. Egyptian Pharmaceutical
Journal 19(1): 67.
10. Elkhateeb WA, Elnahas MO, Thomas PW, Daba GM (2019)
To Heal or Not to Heal? Medicinal Mushrooms Wound
Healing Capacities. ARC Journal of Pharmaceutical
Sciences 5(4): 28-35.
11. Elkhateeb WA, Daba GM, Elnahas MO, Thomas PW
Open Access Journal of Pharmaceutical Research
5
Elkhateeb WA and Daba GM. Analytical Method Development and Validation of Tramadol
Hydrochloride by Pharmaceutical Dosage Form by Ultraviolet Spectroscopy. Pharm Res 2021, 5(3):
000249.
Copyright© Elkhateeb WA and Daba GM.
(2019) Anticoagulant capacities of some medicinal
mushrooms. ARC J Pharma Sci 5(4): 1-9.
12. Elkhateeb W, Elnahas MO, Paul W, Daba GM (2020)
Fomes fomentarius and Polyporus squamosus models
of marvel medicinal mushrooms. Biomed Res Rev 3(1):
1-4.
13. Elkhateeb WA, Daba GM (2021) Mycotherapy of the
good and the tasty medicinal mushrooms Lentinus,
Pleurotus, and Tremella.󰨟 Journal of Pharmaceutics and
Pharmacology Research 4(2): 1-6.
14. Elkhateeb WA, Daba GM (2021) The Fascinating Bird’s
Nest Mushroom, Secondary Metabolites and Biological
Activities.󰨟 International Journal of Pharma Research and
Health Sciences 9(1): 3265-3269.
15. Elkhateeb WA, Daba GM, and Gaziea SM (2021) The Anti-
Nemic Potential of Mushroom against Plant-Parasitic
Nematodes, Open Access Journal of Microbiology &
Biotechnology 6(1): 1-6.
16. Elkhateeb WA, Elnahas MO, Thomas PW, Daba GM
(2020) Trametes Versicolor and Dictyophora Indusiata
Champions of Medicinal Mushrooms. Open Access
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000249.
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... Edible mushrooms are an excellent source of proteins, minerals, polysaccharides, unsaturated fatty acids, and secondary metabolites [11][12][13][14][15][16][17][18][19]. Numerous studies have provided evidence for the protective effects of edible mushrooms against various chronic diseases [20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Mushrooms have provided food for millennia and production methods and species diversity have recently expanded. ...
... Many researches indicate vitamin D as a promising defensive or therapeutic agent against COVID, making this review more vital and important. Mushrooms, as a rich source of vitamin D along with various bioactive compounds [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19], perform a significant role in resolving health issues [20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Mushroom-based medicinal formulations and functional foods serve to deliver vitamins and nutrients to humans, thus helping in health problems, especially in developing countries. ...
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Vitamin D is one of the most important vitamins to human health as it plays a significant role in human's various physiological functions including metabolism of phosphorus and calcium, neuromuscular and skeletal homeostasis and is also effective against various diseases. Although it is found in two major forms, vitamin D 3 (from animal-derived products) and vitamin D 2 (from plant, mushrooms and yeast), it is reported that vitamin D 2 functions similar to vitamin D3 as both possess the ability to improve overall vitamin D levels in blood. Also, vitamin D 2 obtained from mushrooms do not show hypercalcaemic effects reported during the use of vitamin D 3. Hence, we aimed in this study to put mushrooms as a potential source of dietary vitamin D under the spot. Moreover, we mentioned examples of mushroom species reported to contain vitamin D in their composition. Some factors controlling the level of vitamin D in these mushrooms were also highlighted.
... Mushrooms have been used in many sides of human activity for many years. Some of these mushrooms have been called medicinal mushrooms due to their various morphological, physiological, and ecological characteristics that are also responsible for their diversity [20][21][22][23][24][25][26][27][28][29]. Some mushrooms and other fruiting bodies of fi lamentous fungi are edible and provide a good source of protein, whereas others have narcotic eff ects and used as medicine. ...
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Mushrooms are substantial source of nutritional, medicinal compounds, and other benefi ts compounds still need to be worked out for their important applications. Mushrooms as higher Basidiomycetes and Ascomycetes contain secondary metabolites in their fruit bodies, cultured mycelium, and cultured broth. These secondary metabolites have been used in many sides of human activity for many years for maintaining long and healthy life. The genera Pholiota, Pleurotus and Lyophyllum are a group of edible mushrooms that are distributed all over the world. The studies on different species of these edible mushrooms have revealed their nutritional medicinal potentials. This review aims to present the importance of Pholiota microspore, Pleurotus ostreatus and Lyophyllum shimeji, as both food and medicine, and they offer new visions to researchers to develop new drugs and nutraceuticals.
... Due to the diverse morphological, physiological, and ecological traits that also contribute to their diversity, several of these mushrooms have been dubbed medicinal mushrooms [16][17][18][19][20]. Researchers have recently focused more on the uses of mushrooms for food and medicine. Certain mushrooms and other filamentous fungi's fruiting bodies are edible or non-edible in the wild, and they are a good source of many secondary metabolites with therapeutic benefits [21][22][23][24][25]. With a high level of proteins, vitamins, minerals, fibers, and trace elements as well as minimal or no calories and cholesterol, mushrooms have a rich nutritional value. ...
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... Mushrooms are also rich sources of antioxidant vitamins. The ascorbic acid content of certain species of wild edible mushrooms was found to be higher than in some fruits and vegetables [26][27][28][29][30][31][32][33][34]. Ganoderma is a historical fungus that used for promoting health and longevity in China, Japan, and other Asian countries. ...
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Plant-parasitic nematodes are responsible for huge annual economic loss that is estimated to be more than 215 billion US$ worldwide due to plants damages caused by nematodes. The root-knot nematode (Meloidogyne spp.) is ranked first in the global list of top ten plant-parasitic nematodes, with wide host range of more than 3000 host plant species and posing a major threat in the cultivation of agricultural, vegetables, and horticultural crops. Such pathogens are commonly controlled using chemical nematicides. However, the risk of using such chemicals on human, animals, and surrounding environment has forced researchers to search for natural, less harmful, and effective nematicidal agents. In this review, we discuss the biological control of nematodes by different microorganisms, stressing on the promising capabilities of some mushrooms such as some species of Pleurotus, Beauveria, Ganoderma lucidum, and Lentinus edodes.
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Background: Mushrooms are generous source of nutritional and medicinal compounds. Bird's nest fungi are a gasteromyceteous group of mushrooms named for their similarity in shape to small bird's nests. They are considered from the tiniest and most interesting mushrooms all over the world. It is usually found in shady moist environments, and typically survive on plant debris, soil, decaying wood, or animal's excrement. Bird's nest mushrooms are inedible, though they were not previously reported to be poisonous, due to their tiny size. Object: this review aims to put bird's nest mushrooms under light spot through describing their morphology and ecology especially of the most common fungus, Cyathus haller. Moreover, discussing important secondary metabolites and biological activities exerted by bird's nest mushrooms. Conclusion: bird's nest mushrooms are able to produce many novel and potent secondary metabolites that exerted different bioactivities especially as antimicrobial, antitumor, and anti-neuro inflammation activities. Further studies and investigations are encouraged in order to find more about this interesting tiny mushroom.
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Mushrooms, its a natural gift for all living things, because it was a highly lifetime potential and very useful to several ways like, Pharma industries, Agriculture and Allied industries with food sector also. We do not know the full bio-ecological surveillance, biology of mushrooms and its uses. In this book described about importance, biology and how to cultivate mushrooms and preserved it for commercial purposes and adding the knowledge about poisonous mushrooms and how we know that. Finally, in future the gene editing technologies were implemented for desirable for upcoming new ones within next fifty years.
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