Medicinal uses of fungi

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Medicinal fungi are fungi that contain metabolites or can be induced to produce metabolites through biotechnology to develop prescription drugs. Compounds successfully developed into drugs or under research include antibiotics, anti-cancer drugs, cholesterol and ergosterol synthesis inhibitors, psychotropic drugs, immunosuppressants and fungicides.

Contents

History

Although fungi products have long been used in traditional medicine, the ability to identify beneficial properties and then extract the active ingredient started with the discovery of penicillin by Alexander Fleming in 1928. [1] Since that time, many potential antibiotics were discovered and the potential for various fungi to synthesize biologically active molecules useful in various clinical therapies has been under research. Pharmacological research identified antifungal, antiviral, and antiprotozoan compounds from fungi. [2]

Ganoderma lucidum , known in Chinese as líng zhī ("spirit plant"), and in Japanese as mannentake ("10,000-year mushroom"), has been well studied.[ citation needed ] Another species of genus Ganoderma , G. applanatum , remains under basic research.[ citation needed ] Inonotus obliquus was used in Russia as early as the 16th century; it featured in Alexandr Solzhenitsyn's 1967 novel Cancer Ward . [3]

Research and drug development

Cancer

There is no good evidence that any type of mushroom or mushroom extract can prevent or cure cancer. [4] [ better source needed ]


11,11'-Dideoxyverticillin A, an isolate of marine Penicillium, was used to create dozens of semi-synthetic, candidate anticancer compounds. [5] 11,11'-Dideoxyverticillin A, andrastin A, barceloneic acid A, and barceloneic acid B, are farnesyl transferase inhibitors that can be made by Penicillium. [6] 3-O-Methylfunicone, anicequol, duclauxin, and rubratoxin B, are anticancer/cytotoxic metabolites of Penicillium.[ citation needed ]

Penicillium is a potential source of the leukemia medicine asparaginase. [7]

Some countries have approved beta-glucan fungal extracts lentinan, polysaccharide-K, and polysaccharide peptide as immunologic adjuvants. [8]

Antibacterial agents (antibiotics)

Alexander Fleming led the way to the beta-lactam antibiotics with the Penicillium mold and penicillin. Subsequent discoveries included alamethicin, aphidicolin, brefeldin A, cephalosporin, [9] cerulenin, citromycin, eupenifeldin, fumagillin, [9] fusafungine, fusidic acid, [9] helvolic acid, [9] itaconic acid, MT81, nigrosporin B, usnic acid, verrucarin A, vermiculine and many others.

Ling Zhi-8, an immunomodulatory protein isolated from Ganoderma lucidum Ling Zhi-8.png
Ling Zhi-8, an immunomodulatory protein isolated from Ganoderma lucidum

Antibiotics retapamulin, tiamulin, and valnemulin are derivatives of the fungal metabolite pleuromutilin. Plectasin, austrocortilutein, austrocortirubin, coprinol, oudemansin A, strobilurin, illudin, pterulone, and sparassol are under research for their potential antibiotic activity.[ citation needed ]

Cholesterol biosynthesis inhibitors

The red yeast rice fungus, Monascus purpureus, can synthesize three statins. Red yeast rice.jpg
The red yeast rice fungus, Monascus purpureus , can synthesize three statins.

Statins are an important class of cholesterol-lowering drugs; the first generation of statins were derived from fungi. [10] Lovastatin, the first commercial statin, was extracted from a fermentation broth of Aspergillus terreus . [10] Industrial production is now capable of producing 70 mg lovastatin per kilogram of substrate. [11] The red yeast rice fungus, Monascus purpureus , can synthesize lovastatin, mevastatin, and the simvastatin precursor monacolin J. Nicotinamide riboside, a cholesterol biosynthesis inhibitor, is made by Saccharomyces cerevisiae .[ citation needed ]

Antifungals

Some antifungals are derived or extracted from other fungal species. Griseofulvin is derived from a number of Penicillium species; [12] caspofungin is derived from Glarea lozoyensis . [13] Strobilurin, azoxystrobin, micafungin, and echinocandins, are all extracted from fungi. Anidulafungin is a derivative of an Aspergillus metabolite.[ citation needed ]

Antivirals

Many mushrooms contain potential antiviral compounds remaining under preliminary research, such as: Lentinus edodes, Ganoderma lucidum, Ganoderma colossus, Hypsizygus marmoreus, Cordyceps militaris, Grifola frondosa, Scleroderma citrinum,Flammulina velutipes, and Trametes versicolor, Fomitopsis officinalis. [14] [15] [16] [17]

Immunosuppressants

Cyclosporin was discovered in Tolypocladium inflatum , while Bredinin was found in Eupenicillium brefeldianum and mycophenolic acid in Penicillium stoloniferum. Thermophilic fungi were the source of the fingolimod precursor myriocin. Aspergillus synthesizes immunosuppressants gliotoxin and endocrocin. Subglutinols are immunosuppressants isolated from Fusarium subglutinans . [18]

Malaria

Codinaeopsin, efrapeptins, zervamicins, and antiamoebin are made by fungi, and remain under basic research. [19]

Diabetes

Many fungal isolates act as DPP-4 inhibitors, alpha-glucosidase inhibitors, and alpha amylase inhibitors in laboratory studies. Ternatin is a fungal isolate that may affect hyperglycemia. [20]

Psychotropic effects

Numerous fungi have well-documented psychotropic effects, some of them severe and associated with acute and life-threatening side-effects. [21] Among these is Amanita muscaria, the fly agaric. More widely used informally are a range of fungi collectively known as "magic mushrooms", which contain psilocybin and psilocin. [21]

The history of bread-making records deadly ergotism caused by ergot, most commonly Claviceps purpurea , a parasite of cereal crops. [22] [23] Psychoactive ergot alkaloid drugs have subsequently been extracted from or synthesised starting from ergot; these include ergotamine, dihydroergotamine, ergometrine, ergocristine, ergocryptine, ergocornine, methysergide, bromocriptine, cabergoline, and pergolide. [22] [24]

Vitamin D2

The photochemistry of vitamin D2 biosynthesis Vitamin D biosynthesis in fungi and animals.svg
The photochemistry of vitamin D2 biosynthesis

Fungi are a source of ergosterol which can be converted to vitamin D2 upon exposure to ultraviolet light. [25] [26] [27]

Yeasts

The yeast Saccharomyces is used industrially to produce the amino acid lysine, as well as recombinant proteins insulin and hepatitis B surface antigen. Transgenic yeasts are used to produce artemisinin, as well as insulin analogs. [28] Candida is used industrially to produce vitamins ascorbic acid and riboflavin. Pichia is used to produce the amino acid tryptophan and the vitamin pyridoxine. Rhodotorula is used to produce the amino acid phenylalanine. Moniliella is used industrially to produce the sugar alcohol erythritol.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Mold</span> Wooly, dust-like fungal structure or substance

A mold or mould is one of the structures that certain fungi can form. The dust-like, colored appearance of molds is due to the formation of spores containing fungal secondary metabolites. The spores are the dispersal units of the fungi. Not all fungi form molds. Some fungi form mushrooms; others grow as single cells and are called microfungi.

<i>Penicillium</i> Genus of fungi

Penicillium is a genus of ascomycetous fungi that is part of the mycobiome of many species and is of major importance in the natural environment, in food spoilage, and in food and drug production.

<span class="mw-page-title-main">Secondary metabolite</span> Type of organic compound

Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the normal growth, development, or reproduction of the organism. Instead, they generally mediate ecological interactions, which may produce a selective advantage for the organism by increasing its survivability or fecundity. Specific secondary metabolites are often restricted to a narrow set of species within a phylogenetic group. Secondary metabolites often play an important role in plant defense against herbivory and other interspecies defenses. Humans use secondary metabolites as medicines, flavourings, pigments, and recreational drugs.

A mycotoxin is a toxic secondary metabolite produced by fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' is usually reserved for the toxic chemical products produced by fungi that readily colonize crops.

<span class="mw-page-title-main">Lovastatin</span> Chemical compound

Lovastatin, sold under the brand name Mevacor among others, is a statin medication, to treat high blood cholesterol and reduce the risk of cardiovascular disease. Its use is recommended together with lifestyle changes. It is taken by mouth.

<span class="mw-page-title-main">Ergosterol</span> Chemical compound

Ergosterol (ergosta-5,7,22-trien-3β-ol) is a mycosterol found in cell membranes of fungi and protozoa, serving many of the same functions that cholesterol serves in animal cells. Because many fungi and protozoa cannot survive without ergosterol, the enzymes that synthesize it have become important targets for drug discovery. In human nutrition, ergosterol is a provitamin form of vitamin D2; exposure to ultraviolet (UV) light causes a chemical reaction that produces vitamin D2.

<span class="mw-page-title-main">Natural product</span> Chemical compound or substance produced by a living organism, found in nature

A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical synthesis and have played a central role in the development of the field of organic chemistry by providing challenging synthetic targets. The term natural product has also been extended for commercial purposes to refer to cosmetics, dietary supplements, and foods produced from natural sources without added artificial ingredients.

An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical drugs or diet.

<i>Penicillium roqueforti</i> Species of fungus

Penicillium roqueforti is a common saprotrophic fungus in the genus Penicillium. Widespread in nature, it can be isolated from soil, decaying organic matter, and plants.

<span class="mw-page-title-main">Mevastatin</span> Chemical compound

Mevastatin is a hypolipidemic agent that belongs to the statins class.

<span class="mw-page-title-main">Sclerotium</span> Mycelial mass

A sclerotium, is a compact mass of hardened fungal mycelium containing food reserves. One role of sclerotia is to survive environmental extremes. In some higher fungi such as ergot, sclerotia become detached and remain dormant until favorable growth conditions return. Sclerotia initially were mistaken for individual organisms and described as separate species until Louis René Tulasne proved in 1853 that sclerotia are only a stage in the life cycle of some fungi. Further investigation showed that this stage appears in many fungi belonging to many diverse groups. Sclerotia are important in the understanding of the life cycle and reproduction of fungi, as a food source, as medicine, and in agricultural blight management.

<i>Monascus purpureus</i> Species of fungus

Monascus purpureus is a species of mold that is purplish-red in color. It is also known by the names ang-khak rice mold, corn silage mold, maize silage mold, and rice kernel discoloration.

Biodiversity plays a vital role in maintaining human and animal health because numerous plants, animals, and fungi are used in medicine to produce vital vitamins, painkillers, antibiotics, and other medications. Natural products have been recognized and used as medicines by ancient cultures all around the world. Some animals are also known to self-medicate using plants and other materials available to them.

<span class="mw-page-title-main">Akira Endo (biochemist)</span> Japanese biochemist (born 1933)

Akira Endo is a Japanese biochemist whose research into the relationship between fungi and cholesterol biosynthesis led to the development of statin drugs, which are some of the best-selling pharmaceuticals in history.

<i>Ganoderma applanatum</i> Species of fungus

Ganoderma applanatum is a bracket fungus with a cosmopolitan distribution.

<i>Aspergillus terreus</i> Species of fungus

Aspergillus terreus, also known as Aspergillus terrestris, is a fungus (mold) found worldwide in soil. Although thought to be strictly asexual until recently, A. terreus is now known to be capable of sexual reproduction. This saprotrophic fungus is prevalent in warmer climates such as tropical and subtropical regions. Aside from being located in soil, A. terreus has also been found in habitats such as decomposing vegetation and dust. A. terreus is commonly used in industry to produce important organic acids, such as itaconic acid and cis-aconitic acid, as well as enzymes, like xylanase. It was also the initial source for the drug mevinolin (lovastatin), a drug for lowering serum cholesterol.

<span class="mw-page-title-main">Fungus</span> Biological kingdom, separate from plants and animals

A fungus is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as one of the traditional eukaryotic kingdoms, along with Animalia, Plantae and either Protista or Protozoa and Chromista.

<span class="mw-page-title-main">Polysaccharide-K</span>

Polysaccharide-K is a protein-bound polysaccharide isolated from the mycelium of Trametes versicolor.

Fungal isolates have been researched for decades. Because fungi often exist in thin mycelial monolayers, with no protective shell, immune system, and limited mobility, they have developed the ability to synthesize a variety of unusual compounds for survival. Researchers have discovered fungal isolates with anticancer, antimicrobial, immunomodulatory, and other bio-active properties. The first statins, β-Lactam antibiotics, as well as a few important antifungals, were discovered in fungi.

<span class="mw-page-title-main">Human interactions with fungi</span> Overview of human–fungi interactions

Human interactions with fungi include both beneficial uses, whether practical or symbolic, and harmful interactions such as when fungi damage crops, timber, food, or are pathogenic to animals.

References

  1. ↑ "Discovery and Development of Penicillin". American Chemical Society, International Historic Chemical Landmarks. 2020. Retrieved 11 March 2020.
  2. ↑ Engler M, Anke T, Sterner O (1998). "Production of antibiotics by Collybia nivalis, Omphalotus olearis, a Favolaschia and a Pterula species on natural substrates". Zeitschrift für Naturforschung C. 53 (5–6): 318–24. doi: 10.1515/znc-1998-5-604 . PMID   9705612. S2CID   7189999.
  3. ↑ Zheng W, Miao K, Liu Y, Zhao Y, Zhang M, Pan S, Dai Y (July 2010). "Chemical diversity of biologically active metabolites in the sclerotia of Inonotus obliquus and submerged culture strategies for up-regulating their production". Applied Microbiology and Biotechnology. 87 (4): 1237–54. doi: 10.1007/s00253-010-2682-4 . PMID   20532760. S2CID   22145043.
  4. ↑ "Medicinal mushrooms in cancer treatment". Cancer Research UK. Retrieved 4 November 2022.
  5. ↑ Trafton, Anne (27 February 2013). "Research update: Chemists find help from nature in fighting cancer". MIT News.
  6. ↑ Overy, David P.; Larsen, Thomas O.; Dalsgaard, Petur W.; Frydenvang, Karla; Phipps, Richard; Munro, Murray H.G.; Christophersen, Carsten (November 2005). "Andrastin A and barceloneic acid metabolites, protein farnesyl transferase inhibitors from Penicillium albocoremium: chemotaxonomic significance and pathological implications". Mycological Research. 109 (11): 1243–1249. doi:10.1017/s0953756205003734. PMID   16279417.
  7. ↑ Shrivastava A, Khan AA, Shrivastav A, Jain SK, Singhal PK (2012). "Kinetic studies of L-asparaginase from Penicillium digitatum". Preparative Biochemistry & Biotechnology. 42 (6): 574–81. doi:10.1080/10826068.2012.672943. PMID   23030468. S2CID   30396788.
  8. ↑ Ina K, Kataoka T, Ando T (June 2013). "The use of lentinan for treating gastric cancer". Anti-Cancer Agents in Medicinal Chemistry. 13 (5): 681–8. doi:10.2174/1871520611313050002. PMC   3664515 . PMID   23092289.
  9. 1 2 3 4 Broadbent, Douglas (July 1966). "Antibiotics Produced by Fungi". The Botanical Review. 32 (3): 219–242. Bibcode:1966BotRv..32..219B. doi:10.1007/BF02858660. JSTOR   4353729. S2CID   23442996.
  10. 1 2 Tobert JA (July 2003). "Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors". Nature Reviews. Drug Discovery. 2 (7): 517–26. doi:10.1038/nrd1112. PMID   12815379. S2CID   3344720.
  11. ↑ Jahromi MF, Liang JB, Ho YW, Mohamad R, Goh YM, Shokryazdan P (2012). "Lovastatin production by Aspergillus terreus using agro-biomass as substrate in solid state fermentation". Journal of Biomedicine & Biotechnology. 2012: 196264. doi: 10.1155/2012/196264 . PMC   3478940 . PMID   23118499.
  12. ↑ Block, Seymour Stanton (2001). Disinfection, Sterilization, and Preservation. Lippincott Williams & Wilkins. p. 631. ISBN   978-0-683-30740-5.
  13. ↑ Richardson, Malcolm D.; Warnock, David W. (2003). Fungal Infection Diagnosis and Management. Wiley. ISBN   978-1-4051-1578-0.
  14. ↑ Pradeep, Prabin; Manju, Vidya; Ahsan, Mohammad Feraz (2019). "Antiviral Potency of Mushroom Constituents". Medicinal Mushrooms. pp. 275–297. doi:10.1007/978-981-13-6382-5_10. ISBN   978-981-13-6381-8. S2CID   181538245.
  15. ↑ Friedman M (November 2016). "Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans". Foods. 5 (4): 80. doi: 10.3390/foods5040080 . PMC   5302426 . PMID   28231175.
  16. ↑ Zhang T, Ye J, Xue C, Wang Y, Liao W, Mao L, et al. (October 2018). "Structural characteristics and bioactive properties of a novel polysaccharide from Flammulina velutipes". Carbohydrate Polymers. 197: 147–156. doi:10.1016/j.carbpol.2018.05.069. PMID   30007599. S2CID   51629395.
  17. ↑ Girometta C (March 2019). "Fomitopsis officinalis in the light of its bioactive metabolites: a review". Mycology. 10 (1): 32–39. doi:10.1080/21501203.2018.1536680. PMC   6394315 . PMID   30834150.
  18. ↑ Kim H, Baker JB, Park Y, Park HB, DeArmond PD, Kim SH, et al. (August 2010). "Total synthesis, assignment of the absolute stereochemistry, and structure-activity relationship studies of subglutinols A and B". Chemistry: An Asian Journal. 5 (8): 1902–10. doi:10.1002/asia.201000147. PMID   20564278.
  19. ↑ Nagaraj G, Uma MV, Shivayogi MS, Balaram H (January 2001). "Antimalarial activities of peptide antibiotics isolated from fungi". Antimicrobial Agents and Chemotherapy. 45 (1): 145–9. doi:10.1128/aac.45.1.145-149.2001. PMC   90252 . PMID   11120957.
  20. ↑ Lo HC, Wasser SP (2011). "Medicinal mushrooms for glycemic control in diabetes mellitus: history, current status, future perspectives, and unsolved problems (review)". International Journal of Medicinal Mushrooms. 13 (5): 401–26. doi:10.1615/intjmedmushr.v13.i5.10. PMID   22324407.
  21. 1 2 "Hallucinogenic mushrooms drug profile". The European Monitoring Centre for Drugs and Drug Addiction.
  22. 1 2 Schiff, Paul L. (September 2006). "Ergot and Its Alkaloids". American Journal of Pharmaceutical Education. 70 (5): 98. doi:10.5688/aj700598. PMC   1637017 . PMID   17149427.
  23. ↑ Shiel, William C. "Medical Definition of Ergotism". MedicineNet. Retrieved 18 October 2020.
  24. ↑ Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E (January 2007). "Dopamine agonists and the risk of cardiac-valve regurgitation". The New England Journal of Medicine. 356 (1): 29–38. doi: 10.1056/NEJMoa062222 . PMID   17202453.
  25. ↑ Keegan RJ, Lu Z, Bogusz JM, Williams JE, Holick MF (January 2013). "Photobiology of vitamin D in mushrooms and its bioavailability in humans". Dermato-Endocrinology. 5 (1): 165–76. doi:10.4161/derm.23321. PMC   3897585 . PMID   24494050.
  26. ↑ Kamweru PK, Tindibale EL (2016). "Vitamin D and Vitamin D from Ultraviolet-Irradiated Mushrooms (Review)". International Journal of Medicinal Mushrooms. 18 (3): 205–14. doi:10.1615/IntJMedMushrooms.v18.i3.30. PMID   27481154.
  27. ↑ Cardwell, Glenn; Bornman, Janet; James, Anthony; Black, Lucinda (13 October 2018). "A Review of Mushrooms as a Potential Source of Dietary Vitamin D". Nutrients. 10 (10): 1498. doi: 10.3390/nu10101498 . PMC   6213178 . PMID   30322118.
  28. ↑ Peplow, Mark (16 April 2013). "Sanofi launches malaria drug production". Chemistry World.
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