Medicinal molds

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Aspergillus

Medicinal molds are fungi used for biotechnology or drug discovery. Because molds typically exist as thin mycelial monolayers, with no protective shell, immune system, or much mobility, they rely on an ability to synthesize a variety of unusual compounds for survival. Researchers have discovered important medicines from molds, like penicillin and lovastatin. The biotechnological potential of molds is clearly illustrated with Penicillium raistrickii-derived paclitaxel.

Anticancer compounds[edit]

Medicinal molds that synthesize paclitaxel, were discovered in Taxus (left), Corylus[1] (center), and Cardiospermum halicacabum[2] (right)

Bristol-Myers Squibb manufactures paclitaxel using Penicillium raistrickii and plant cell fermentation (PCF). Fungi can synthesize other mitotic inhibitors including vinblastine, vincristine, podophyllotoxin, griseofulvin, aurantiamine, oxaline, and neoxaline.[3]

11,11'-Dideoxyverticillin A, an isolate of marine Penicillium, was used to create dozens of semi-synthetic anticancer compounds.[4] 11,11'-Dideoxyverticillin A, andrastin A, barceloneic acid A, and barceloneic acid B, are farnesyl transferase inhibitors that can be made by Penicillium.[5] 3-O-Methylfunicone, anicequol, duclauxin, and rubratoxin B, are anticancer/cytotoxic metabolites of Penicillium.

Penicillium is a potential source of the leukemia medicine asparaginase (Erwinaze).[6]

Antibiotics[edit]

Rhizopus oligosporus produces tempeh, as well as a cystine rich antibiotic[7]

Alexander Fleming led the way to the beta-lactam antibiotics with the Penicillium mold and penicillin. Cephalosporin, fusafungine, fumagillin, alamethicin, fusidic acid, aphidicolin, cerulenin, brefeldin A, verrucarin A, itaconic acid, aphidicolin, nigrosporin B, eupenifeldin, vermiculine, citromycin, MT81, and citric acid, can be synthesized by molds.

Cholesterol biosynthesis inhibitors[edit]

Monascus purpureus produces red yeast rice, as well as three different types of statins

Akira Endo led the way to the statin medications isolating the pravastatin precursor mevastatin from Penicillium. Lovastatin, the first commercial statin, was found in the Aspergillus mold. Aspergillus is capable of producing 70mg lovastatin per kilogram of substrate.[8]

The red yeast rice mold, Monascus purpureus, creates lovastatin, mevastatin, and the simvastatin precursor monacolin J. Zaragozic acids were isolated from ascomycota. Nicotinamide riboside, a cholesterol biosynthesis inhibitor, is made by Saccharomyces cerevisiae.

Antifungals[edit]

Griseofulvin, caspofungin, strobilurin, azoxystrobin, micafungin, and echinocandins, were discovered in molds. Anidulafungin is a derivative of an Aspergillus metabolite.

Immunosuppressants[edit]

Ciclosporin, was discovered in Tolypocladium inflatum. Bredinin was discovered in Eupenicillium brefeldianum. Mycophenolic acid was discovered in Penicillium stoloniferum. Thermophilic molds were the source of the fingolimod precursor myriocin. Aspergillus synthesizes immunosuppressants gliotoxin and endocrocin.

Antimalarials[edit]

Fungal isolates codinaeopsin, efrapeptins, zervamicins, and antiamoebin, inhibit malaria protozoa.

Antidiabetic compounds[edit]

Aspergillusol A is an alpha-glucosidase inhibitor made by Aspergillus. Sclerotiorin is an aldose reductase inhibitor made by Penicillium.

Ergoloids[edit]

Aspergillus and Penicillium are potential sources of ergot alkaloid precursors to psychotropic medicines, hydergine (dihydroergocristine, dihydroergocornine, α-, and β-dihydroergocryptine), cafergot, dihydroergotamine, methysergide, methylergometrine, nicergoline, lisuride, bromocriptine, cabergoline, pergolide, as well as bio-active ergolines ergine, ergometrine, lysergic acid, lysergic acid hydroxyethylamide, lysergic acid diethylamide.

Biotechnology[edit]

Fermentek produces apicidin, beauvericin, cytochalasin E, radicicol, K252a, wortmannin, and other pharmaceutical compounds using Penicillium, Aspergillus, and Fusarium. Endophytic fungi are currently used to manufacture paclitaxel.

Endophytic fungi are potential sources of the paclitaxel precursor baccatin III, the docetaxel precursor 10-deacetylbaccatin, vinblastine, vincristine, huperzine A, hypericin, vincamine, gentiopicrin, chlorogenic acid, diosgenin, and ginkgolide B. Endophytic fungi are potential sources of podophyllotoxin and camptothecin, precursors to etoposide, teniposide, topotecan, and irinotecan.

Mycelium can be used to biosynthesize gold nanoparticles and be used as a mycofiltrate to recover gold from electronic waste.[9][10][1] Aspergillus can metabolize piceid to resveratrol.[11]

Transgene-based biotechnology[edit]

The introduction and expression of the fungal gene responsible for synthesizing baccatin III, to the mushroom Flammulina velutipes was recently reported.[12]

Transgenic yeast are used to produce artemisinin, as well as a number of insulin analogs.[13]

See also[edit]

References[edit]

  1. ^ Bemani E, Ghanati F, Rezaei A, Jamshidi M (2013). "Effect of phenylalanine on Taxol production and antioxidant activity of extracts of suspension-cultured hazel (Corylus avellana L.) cells.". J Nat Med 67 (3): 446–51. doi:10.1007/s11418-012-0696-1. PMID 22847380. 
  2. ^ Gangadevi V, Murugan M, Muthumary J (2008). "Taxol determination from Pestalotiopsis pauciseta, a fungal endophyte of a medicinal plant.". Sheng Wu Gong Cheng Xue Bao 24 (8): 1433–8. PMID 18998547. 
  3. ^ http://www.globalsciencebooks.info/JournalsSup/images/0806/IJBPS_2%281%291-23o.pdf
  4. ^ "Research update: Chemists find help from nature in fighting cancer - MIT News Office". Web.mit.edu. 2013-02-27. Retrieved 2013-12-17. 
  5. ^ Overy DP, Larsen TO, Dalsgaard PW, Frydenvang K, Phipps R, Munro MH et al. (2005). "Andrastin A and barceloneic acid metabolites, protein farnesyl transferase inhibitors from Penicillium albocoremium: chemotaxonomic significance and pathological implications.". Mycol Res 109 (Pt 11): 1243–9. PMID 16279417. 
  6. ^ Shrivastava A, Khan AA, Shrivastav A, Jain SK, Singhal PK (2012). "Kinetic studies of L-asparaginase from Penicillium digitatum.". Prep Biochem Biotechnol 42 (6): 574–81. doi:10.1080/10826068.2012.672943. PMID 23030468. 
  7. ^ Kobayasi S, Okazaki N, Koseki T (1992). "Purification and characterization of an antibiotic substance produced from Rhizopus oligosporus IFO 8631.". Biosci Biotechnol Biochem 56 (1): 94–8. PMID 1368137. 
  8. ^ 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.". J Biomed Biotechnol 2012: 196264. doi:10.1155/2012/196264. PMC 3478940. PMID 23118499. 
  9. ^ Li G, He D, Qian Y, Guan B, Gao S, Cui Y et al. (2012). "Fungus-Mediated Green Synthesis of Silver Nanoparticles Using Aspergillus terreus.". Int J Mol Sci 13 (1): 466–76. doi:10.3390/ijms13010466. PMC 3269698. PMID 22312264. 
  10. ^ Gupta S, Bector S (2013). "Biosynthesis of extracellular and intracellular gold nanoparticles by Aspergillus fumigatus and A. flavus.". Antonie Van Leeuwenhoek 103 (5): 1113–23. doi:10.1007/s10482-013-9892-6. PMID 23400423. 
  11. ^ Wang H, Liu L, Guo YX, Dong YS, Zhang DJ, Xiu ZL (2007). "Biotransformation of piceid in Polygonum cuspidatum to resveratrol by Aspergillus oryzae.". Appl Microbiol Biotechnol 75 (4): 763–8. doi:10.1007/s00253-007-0874-3. PMID 17333175. 
  12. ^ Han F, Kang LZ, Zeng XL, Ye ZW, Guo LQ, Lin JF (2014). "Bioproduction of baccatin III, an advanced precursor of paclitaxol with transgenic Flammulina velutipes expressing 10-Deacetylbaccatin III-10-O-acetyl transferase gene.". J Sci Food Agric. doi:10.1002/jsfa.6562. PMID 24403190. 
  13. ^ Mark Peplow. "Sanofi launches malaria drug production | Chemistry World". Rsc.org. Retrieved 2013-12-17. 

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