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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.

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]

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

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.

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

Main article: Psilocybin mushroom

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

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]

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. ^ a b c d Broadbent, Douglas (July 1966). "Antibiotics Produced by Fungi". The Botanical Review. 32 (3): 219–242. doi:10.1007/BF02858660. JSTOR 4353729. S2CID 23442996.
  10. ^ a b 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. ^ a b "Hallucinogenic mushrooms drug profile". The European Monitoring Centre for Drugs and Drug Addiction.
  22. ^ a b 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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