Fungal Diversity

, 50:3 | Cite as

Fifty years of drug discovery from fungi



For the past 50 years, fungal secondary metabolites have revolutionized medicine yielding blockbuster drugs and drug leads of enormous therapeutic and agricultural potential. Since the discovery of penicillin, the first β-lactam antibiotic, fungi provided modern medicine with important antibiotics for curing life threatening infectious diseases. A new era in immunopharmacology and organ transplantation began with the discovery of cyclosporine. Other important drugs or products for agriculture derived from or inspired by natural products from fungi include statins, echinocandins and strobilurins. Moreover, fungal biotransformation of steroids for the industrial production of steroidal hormones represents one of the key successes in biotechnology. Given that estimations of fungal biodiversity exceed by far the number of already identified species, chances to find hitherto unidentified fungal species and novel bioactive fungal products are still high. Thus, further compounds with medicinal or agricultural potential from less investigated fungal taxa can be expected in the years to come.


Drug discovery Fungi Bioactive metabolites 



Continued support by BMBF to P.P. is gratefully acknowledged.


  1. Abraham E (1990) Selective reminiscences of beta-lactam antibiotics: early research on penicillin and cephalosporins. Bioessays 12:601–606PubMedGoogle Scholar
  2. Abraham EP, Chain E, Fletcher CM, Gardner AD, Heatley NG, Jennings MA, Florey HW (1941) Further observations on penicillin. Lancet 238:177–189Google Scholar
  3. Ago H, Oda M, Takahashi M, Tsuge H, Ochi S, Katunuma N, Miyano M, Sakurai J (2006) Structural basis of the sphingomyelin phosphodiesterase activity in neutral sphingomyelinase from Bacillus cereus. J Biol Chem 281:16157–16167PubMedGoogle Scholar
  4. Ahmed F, Williams RA, Smith KE (1996) Microbial transformations of steroids—X. Cytochromes P-450 11 alpha-hydroxylase and C17-C20 lyase and a 1-ene dehydrogenase transform steroids in Nectria haematococca. J Steroid Biochem Mol Biol 58:337–349PubMedGoogle Scholar
  5. Alanis AJ (2005) Resistance to antibiotics: are we in the post-antibiotic era? Arch Med Res 36:697–705PubMedGoogle Scholar
  6. Alberts AW (1988) Discovery, biochemistry and biology of lovastatin. Am J Cardiol 62:10J–15JPubMedGoogle Scholar
  7. Alberts AW, Chen J, Kuron G, Hunt V, Huff J, Hoffman C, Rothrock J, Lopez M, Joshua H, Harris E, Patchett A, Monaghan R, Currie S, Stapley E, Albers-Schonberg G, Hensens O, Hirshfield J, Hoogsteen K, Liesch J, Springer J (1980) Mevinolin: a high potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci USA 77:3957–3961PubMedGoogle Scholar
  8. Aly AH, Debbab A, Kjer J, Proksch P (2010) Fungal endophytes from higher plants: a prolific source of phytochemicals and other bioactive natural products. Fungal Divers 41:1–16Google Scholar
  9. Ammermann E, Lorenz G, Schelberger K, Wenderoth B, Sauter H, Rentzea C (1992) Brighton Crop Prot Conf: pests and diseases. British Crop Protection Council, Farnham, p 403Google Scholar
  10. Ammermann E, Lorenz G, Schelberger K, Mueller B, Kirstgen R, Sauter H (2000) BAS 500 F—the new broad-spectrum strobilurin fungicide. In: Proc Brighton Crop Protect Conf: Pests and Diseases. British Crop Protection Council, Farnham, UK, pp 541–548Google Scholar
  11. Anderson JD (1980) Fusidic acid: new opportunities with an old antibiotic. Can Med Assoc J 122:765–769PubMedGoogle Scholar
  12. Anke T (1995) The antifungal strobilurins and their possible ecological role. Can J Bot 73:S940–S945Google Scholar
  13. Anke T, Thines E (2007) Fungal metabolites as lead structures for agriculture. In: Robson GD, Van West P, Gadd GM (eds) Exploitation of fungi. Cambridge University Press, Cambridge, pp 45–58Google Scholar
  14. Anke T, Oberwinkler F, Steglich W, Schramm G (1977) The strobilurins—new antifungal antibiotics from the basidiomycete Strobilurus tenacellus. J Antibiot 30:806–810PubMedGoogle Scholar
  15. Anke T, Hecht HJ, Schramm G, Steglich W (1979) Antibiotics from basidiornycetes. IX. Oudemansin, an antifungal antibiotic from Oudemansiella mucida (Schrader ex Fr.) Hoehnel (Agaricales). J Antibiot 32:1112–1117PubMedGoogle Scholar
  16. Anke T, Besl H, Mocek U, Steglich W (1983) Antibiotics from basidiomycetes. XVIII. Strobilurin C and oudemansin B, two new antifungal metabolites from Xerula species (Agaricales). J Antibiot 36:661–666PubMedGoogle Scholar
  17. Appel J, Felsenstein FG (2000) Entwicklung der Strobilurinresistenz des Weizenmehltaus in Europa in den Jahren 1998 bis 2000. Mitt Biol Bundesanst 376:97Google Scholar
  18. Barry AL, Jones RN (1987) In vitro activity of ciprofloxacin against gram-positive cocci. Am J Med 82:27–32PubMedGoogle Scholar
  19. Bartett DW, Clough JM, Godfrey CRA, Godwin JR, Hall AA, Heaney SP, Maund SJ (2001) Understanding the strobilurin fungicides. Pestic Outlook 12:143–148Google Scholar
  20. Beautement K, Clough JM (1987) Stereocontrolled syntheses of strobilurin A and its (9E)-isomer. Tetrahedron Lett 28:475–478Google Scholar
  21. Becker WF, von Jagow G, Anke T, Steglich W (1981) Oudemansin, strobilurin A, strobilurin B and myxothiazol: new inhibitors of the bc1 segment of the respiratory chain with an E-beta-methoxyacrylate system as common structural element. FEBS Lett 132:329–333PubMedGoogle Scholar
  22. Bergstralh DT, Ting JP (2006) Microtubule stabilizing agents: their molecular signaling consequences and the potential for enhancement by drug combination. Cancer Treat Rev 32:166–179PubMedGoogle Scholar
  23. Black WA, McNellis DA (1971) Comparative in-vitro sensitivity of Nocardia species to fusidic acid and sulphonamides. J Med Microbiol 4:293–295PubMedGoogle Scholar
  24. Blunt JW, Copp BR, Munro MHG, Northcote PT, Prinsep MR (2011) Marine natural products. Nat Prod Rep. doi: 10.1039/C005001F
  25. Borel JF, Kis ZL (1991) The discovery and development of cyclosporine. Transplant Proc 23:1867–1874PubMedGoogle Scholar
  26. Borges KB, Borges WDS, Pupo MT, Bonato PS (2007) Endophytic fungi as models for the stereoselective biotransformation of thioridazine. Appl Microbiol Biotechnol 77:669–674PubMedGoogle Scholar
  27. Bortolini O, Medici A, Poli S (1997) Biotransformations of the steroid nucleus of bile acids. Steroids 62:564–577PubMedGoogle Scholar
  28. Brian PW (1949) Studies on the biological activity of griseofulvin. Ann Bot 13:59–77Google Scholar
  29. Buckland B, Gbewonyo K, Hallada T, Kaplan L, Masurekar P (1989) Production of lovastatin, an inhibitor of cholesterol accumulation in humans. In: Demain AL, Somkuti GA, Hunter-Cevera JC, Rossmore HW (eds) Novel microbial product for medicine and agriculture. Elsevier, Amsterdam, pp 161–169Google Scholar
  30. Bush K, Jacoby G (1997) Nomenclature of TEM β-lactamases. J Antimicrob Chemother 39:1–3PubMedGoogle Scholar
  31. Butler MS (2004) The role of natural product chemistry in drug discovery. J Nat Prod 67:2141–2153PubMedGoogle Scholar
  32. Chadwick AJ, Jackson B (1969) Intraocular penetration of the antibiotic fucidin. Br J Ophthalmol 53:26–29PubMedGoogle Scholar
  33. Chen SCA, Slavin MA, Sorrell TC (2011) Echinocandin antifungal drugs in fungal infections: a comparison. Drugs 71:11–41PubMedGoogle Scholar
  34. Clough JM (2000) The strobilurin fungicides—from mushroom to molecule to market. In: Wrigley SK, Hayes MA, Thomas R, Chrystal EJT, Nicholson N (eds) Biodiversity: new leads for the pharmaceutical and agrochemical industries. The Royal Society of Chemistry, Cambridge, pp 277–282Google Scholar
  35. Conder GA, Johnson SS, Nowakowski DS, Blake TE, Dutton FE, Nelson SJ, Thomas EM, Davis JP, Thompson DP (1995) Anthelmintic profile of the cyclodepsipeptide PF1022A in in vitro and in vivo models. J Antibiot 48:820–823PubMedGoogle Scholar
  36. Crabtree GR (1999) Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT. Cell 96:611–614PubMedGoogle Scholar
  37. Crosbie RB (1963) Treatment of staphylococcal infections with “fucidin”. Br Med J 1:788–794PubMedGoogle Scholar
  38. Cundliffe E (1972) The mode of action of fusidic acid. Biochem Biophys Res Commun 46:1794–1801PubMedGoogle Scholar
  39. Czarny M, Schnitzer JE (2004) Neutral sphingomyelinase inhibitor scyphostatin prevents and ceramide mimics mechanotransduction in vascular endothelium. Am J Physiol Heart Circ Physiol 287:H1344–H1352PubMedGoogle Scholar
  40. Dayan FE, Cantrell CL, Duke SO (2009) Natural products in crop protection. Bioorg Med Chem 17:4022–4034PubMedGoogle Scholar
  41. Demain AL (2000) Small bugs, big business: the economic power of the microbe. Biotechnol Adv 18:499–514PubMedGoogle Scholar
  42. Demain AL, Elander RP (1999) The β-lactam antibiotics: past, present, and future. Antonie Leeuwenhoek 75:5–19PubMedGoogle Scholar
  43. Denning DW (1997) Echinocandins and pneumocandins—a new antifungal class with a novel mode of action. J Antimicrob Chemother 40:611–614PubMedGoogle Scholar
  44. Dewick PM (2006) Medicinal natural products. A biosynthetic approach. Wiley, Baffins LaneGoogle Scholar
  45. Dornetshuber R, Kamyar MR, Rawnduzi P, Baburin I, Kouri K, Pilz E, Hornbogen T, Zocher R, Berger W, Lemmens-Gruber R (2009) Effects of the anthelmintic drug PF1022A on mammalian tissue and cells. Biochem Pharmacol 77:1437–1444PubMedGoogle Scholar
  46. Dowson CG, Hutchison A, Brannigan JA, George RC, Hansman D, Liñares J, Tomasz A, Smith JM, Spratt BG (1989) Horizontal transfer of penicillin-binding protein genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Proc Natl Acad Sci USA 86:8842–8846PubMedGoogle Scholar
  47. Elander RP (2003) Industrial production of β-lactam antibiotics. Appl Microbiol Biotechnol 61:385–392PubMedGoogle Scholar
  48. El-Mekkawy S, Meselhy MR, Nakamura N, Tezuka Y, Hattori M, Kakiuchi N, Shimotohno K, Kawahata T, Otake T (1998) Anti-HIV-1 and anti-HIV-1-protease substances from Ganoderma lucidum. Phytochemistry 49:1651–1657PubMedGoogle Scholar
  49. Elrod J, Wong R, Mishra S, Vagnozzi RJ, Sakthievel B, Goonasekera SA, Karch J, Gabel S, Farber J, Force T, Brown JH, Murphy E, Molkentin JD (2010) Cyclophilin D controls mitochondrial pore-dependent Ca2+ exchange, metabolic flexibility, and propensity for heart failure in mice. J Clin Invest 120:3680–3687PubMedGoogle Scholar
  50. Endo A, Kuroda M, Tsujita Y (1976) ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinium. J Antibiot 29:1346–1348PubMedGoogle Scholar
  51. Faber M, Rosdahl VT (1990) Susceptibility to fusidic acid among Danish Staphylococcus aureus strains and fusidic acid consumption. J Antimicrob Chemother 25:7–14PubMedGoogle Scholar
  52. Falagas ME, Grammatikos AP, Michalopoulos A (2008) Potential of old-generation antibiotics to address current need for new antibiotics. Expert Rev Anti Infect Ther 6:593–600PubMedGoogle Scholar
  53. Fernandes P, Cruz A, Angelova B, Pinheiro HM, Cabral JMS (2003) Microbial conversion of steroid compounds: recent developments. Enzyme Microb Technol 32:688–705Google Scholar
  54. Fleming A (1980) Classics in infectious diseases: on the antibacterial action of cultures of a Penicillium, with special reference to their use in the isolation of B. influenzae by Alexander Fleming, Reprinted from the British Journal of Experimental Pathology 10: 226–236, 1929. Rev Infect Dis 2:129–139PubMedGoogle Scholar
  55. Fredenhagen A, Kuhn A, Peter HH, Cuomo V, Giuliano U (1990) Strobilurins F, G and H, three new antifungal metabolites from Bolinea lutea. I. Fermentation, isolation and biological activity. J Antibiot 43:655–660PubMedGoogle Scholar
  56. Furberg CD (1999) Natural statins and stroke risk. Circulation 99:185–188PubMedGoogle Scholar
  57. Ganong WF (2005) Review of medical physiology, 22nd edn. Lange Medical Books, pp 530Google Scholar
  58. Godtfredsen W, Roholt K, Tybring L (1962a) Fucidin. A new orally active antibiotic. Lancet 279:928–931Google Scholar
  59. Godtfredsen WO, Jahnsen S, Lorck H, Roholt K, Tybring L (1962b) Fusidic acid; a new antibiotic. Nature 193:987PubMedGoogle Scholar
  60. Godtfredsen WO, Von Daehne W, Tybring L, Vangedal S (1966) Fusidic acid derivatives. I. Relationship between structure and antibacterial activity. J Med Chem 9:15–22PubMedGoogle Scholar
  61. Godwin JR, Anthony VM, Clough JM, Godfrey CRA (1992) Brighton Crop Prot Conf: pests and diseases. British Crop Protection Council, Farnham, p 435Google Scholar
  62. Godwin JR, Bartlett DW, Clough JM, Godfrey CRA, Harrison EG, Maund S (2000) Picoxystrobin: a new strobilurin fungicide for use on cereals. In: Proc Brighton Crop Protect Conf: Pests and Diseases. British Crop Protection Council, Farnham, UK, pp 533–540Google Scholar
  63. Griffiths HJ (1978) A handbook of veterinary parasitology: domestic animals of North America. University of Minnesota Press, Minneapolis, pp 46–47Google Scholar
  64. Grove JF, MacMillan J, Mulholland TPC, Rogers MAT (1952) Griseofulvin. Part IV. Structure. J Chem Soc 3977–3987Google Scholar
  65. Guenthner SH, Wenzel RP (1984) In vitro activities of teichomycin, fusidic acid, flucloxacillin, fosfomycin, and vancomycin against methicillinresistant Staphylococcus aureus. Antimicrob Agents Chemother 26:268–269PubMedGoogle Scholar
  66. Gull K, Trinci APJ (1973) Griseofulvin inhibits fungal mitosis. Nature 244:292–294PubMedGoogle Scholar
  67. Gunatilaka AAL (2006) Natural products from plant-associated microorganisms: distribution, structural diversity, bioactivity, and implication of their occurence. J Nat Prod 69:509–526PubMedGoogle Scholar
  68. Hagel I, Giusti T (2010) Ascaris lumbricoides: an overview of therapeutic targets. Infect Disord Drug Targets 10:349–367PubMedGoogle Scholar
  69. Hannun YA, Obeid LM (2002) The ceramide-centric universe of lipid-mediated cell regulation: stress encounters of the lipid kind. J Biol Chem 277:25847–25850PubMedGoogle Scholar
  70. Harder A, Schmitt-Wrede HP, Krücken J, Marinovski P, Wunderlich F, Willson J, Amliwala K, Holden-Dye L, Walker R (2003) Cyclooctadepsipeptides—an anthelmintically active class of compounds exhibiting a novel mode of action. Int J Antimicrob Agents 22:318–331PubMedGoogle Scholar
  71. Hawksworth DL, Rossman AY (1997) Where are all the undescribed fungi? Phytopathology 87:888–891PubMedGoogle Scholar
  72. Hayase Y, Kataoka T, Masuko M, Niikawa M, Ichinari M, Takenaka H, Takahashi T, Hayashi Y, Takeda R (1995) Phenoxyphenyl alkoxyiminoacetamides. New broad-spectrum fungicides. In: Baker DR, Fenyes JG, Basarab GS (eds) Synthesis and chemistry of agrochemicals IV. ACS Symposium Series 584. American Chemical Society, Washington DC, pp 343–353Google Scholar
  73. Hensens OD, Ondeyka JG, Dombrowski AW, Ostlind DA, Zink DL (1999) Isolation and structure of nodulisporic acid A1 and A2, novel insecticides from a Nodulisporium sp. Tetrahedron Lett 40:5455–5458Google Scholar
  74. Ho YS, Duh JS, Jeng JH, Wang YJ, Liang YC, Lin CH, Tseng CJ, Yu CF, Chen RJ, Lin JK (2001) Griseofulvin potentiates antitumorigenesis effects of nocodazole through induction of apoptosis and G2/M cell cycle arrest in human colorectal cancer cells. Int J Cancer 91:393–401PubMedGoogle Scholar
  75. Holliday J, Cleaver M (2008) Medicinal value of the caterpillar fungi species of the genus Cordyceps (Fr.) Link (Ascomycetes): a review. Int J Med Mushr 10:219–234Google Scholar
  76. Holten KB, Onusko EM (2000) Appropriate prescribing of oral beta-lactam antibiotics. Am Fam Physician 62:611–620PubMedGoogle Scholar
  77. Hosokawa T, Inui S, Murahashi SI (1983) Ganoderic acid T and Z: cytotoxic triterpenes from Ganoderma lucidum. Tetrahedron Lett 24:1081–1084Google Scholar
  78. Houchins J, Hind G (1983) Flash spectroscopic characterization of photosynthetic electron transport in isolated heterocysts. Arch Biochem Biophys 224:272–282PubMedGoogle Scholar
  79. Hoye TR, Tennakoon MA (2000) Synthesis (and alternative proof of configuration) of the scyphostatin C(1′)-C(20′) trienoyl fragment. Org Lett 2:1481–1483PubMedGoogle Scholar
  80. Huber FM, Gottlieb D (1968) The mechanism of action of griseofulvin. Can J Microbiol 14:111–118PubMedGoogle Scholar
  81. Hyde KD, Bahkali AH, Moslem MA (2010) Fungi—an unusual source for cosmetics. Fungal Divers 43:1–9Google Scholar
  82. IMS Health (2005) Annual Report on prescription drug trends.
  83. IMS Health (2008) Annual Report on prescription drug trends.
  84. Irrgang S, Schlosser D, Fritsche W (1997) Involvement of cytochrome P-450 in the 15alpha-hydroxylation of 13-ethyl-gon-4-ene-3,17-dione by Penicillium raistrickii. J Steroid Biochem Mol Biol 60:339–346PubMedGoogle Scholar
  85. Ishii H, Fraaije BA, Sugiyama T, Noguchi K, Nishimura K, Takeda T, Amano T, Hollomon DW (2001) Occurrence and molecular characterization of strobilurin resistance in cucumber powdery mildew and downy mildew. Phytopathology 91:1166–1171PubMedGoogle Scholar
  86. Izuhara T, Katoh T (2001) Studies toward the total synthesis of scyphostatin: first entry to the highly functionalized cyclohexenone segment. Org Lett 3:1653–1656PubMedGoogle Scholar
  87. Jeschke P, Harder A, Etzel W, Gau W, Thielking G, Bonse G, Iinuma K (2001) Synthesis and anthelmintic activity of thioamide analogues of cyclic octadepsipeptides such as PF1022A. Pest Manag Sci 57:1000–1006PubMedGoogle Scholar
  88. Jiang MY, Feng T, Liu JK (2011) N-containing compounds of macromycetes. Nat Prod Rep 28:783–808PubMedGoogle Scholar
  89. Kanski JJ (1974) Treatment of late endophthalmitis associated with filtering blebs. Arch Ophthalmol 91:339–343PubMedGoogle Scholar
  90. Keller-Juslen C, Kuhn M, Loosli H-R, Pechter TJ, von Weber HP, Wartburg A (1976) Structure des cyclopeptideantibiotikum SL 7810 (Echinocandin B). Tetrahedron Lett 17:4147–4150Google Scholar
  91. Khan MA, Tania M, Zhang DZ, Chen HC (2010) Cordyceps mushroom: a potent anticancer nutraceutical. Open Nutraceuticals J 3:179–183Google Scholar
  92. Kharwar RN, Mishra A, Gond SK, Stierle A, Stierle D (2011) Anticancer compounds derived from fungal endophytes: their importance and future challenges. Nat Prod Rep. doi: 10.1039/C1NP00008J
  93. Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK (2007) Invasive methicillin-resistant Staphylococcus aureus infections in the United States. J Am Med Assoc 298:1763–1771Google Scholar
  94. Koehn FE (2009) Drug discovery from natural products. Nature 8:678Google Scholar
  95. Koester DH (1937) United States Patent 2, 236, 574Google Scholar
  96. Kolesnick R, Golde DW (1994) The sphingomyelin pathway in tumor necrosis factor and interleukin-1 signaling. Cell 77:325–328PubMedGoogle Scholar
  97. Kubota T, Asaka Y, Miura I, Mori H (1982) Structures of ganoderic acid A and B, two new lanostane type bitter triterpenes from Ganoderma lucidum (Fr.) Karst. Helv Chim Acta 65:611–619Google Scholar
  98. Larsen TO, Smedsgaard J, Nielsen KF, Hansen ME, Frisvad JC (2005) Phenotypic taxonomy and metabolite profiling in microbial drug discovery. Nat Prod Rep 22:672–695PubMedGoogle Scholar
  99. Law MR, Wald NJ, Rudnicka AR (2003) Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. Br Med J 326:1423–1429Google Scholar
  100. Lee BH, Dutton FE, Thompson DP, Thomas EM (2002) Generation of a small library of cyclodepsipeptide PF1022A analogues using a cyclization-cleavage method with oxime resin. Bioorg Med Chem Lett 12:353–356PubMedGoogle Scholar
  101. Leigh DA (1974) Clinical importance of infections due to Bacteroides fragilis and role of antibiotic therapy. Br Med J 3:225–228PubMedGoogle Scholar
  102. Lesemann SS, Schimpke S, Dunemann F, Deising HB (2006) Mitochondrial heteroplasmy for the cytochrome b gene controls the level of strobilurin resistance in the apple powdery mildew fungus Podosphaera leucotricha (Ell. & Ev.) E.S. Salmon. J Plant Dis Protect 113:259–266Google Scholar
  103. Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R, Collins R (2007) Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 370:1829–1839PubMedGoogle Scholar
  104. Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, Michelassi F, Hanauer S (1994) Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med 330:1841–1845PubMedGoogle Scholar
  105. Lindequist U, Rausch R, Füssel A, Hanssen HP (2010) Higher fungi in traditional and modern medicine. Med Monatsschr Pharm 33:40–48PubMedGoogle Scholar
  106. MacGowan AP, Greig MA, Andrews JM, Reeves DS, Wise R (1989) Pharmacokinetics and tolerance of a new film-coated tablet of sodium fusidate administered as a single oral dose to healthy volunteers. J Antimicrob Chemother 23:409–415PubMedGoogle Scholar
  107. Mahato SB, Banerjee S (1985) Steroid transformation by microorganisms II. Phytochemistry 24:1403–1421Google Scholar
  108. Mahato SB, Garai S (1997) Advances in microbial steroid biotransformation. Steroids 62:332–345PubMedGoogle Scholar
  109. Mahato SB, Mukherjee A (1984) Steroid transformations by microorganisms. Phytochemistry 23:2131–2154Google Scholar
  110. Maksay G, Laube B, Betz H (2001) Subunit-specific modulation of glycine receptors by neurosteroids. Neuropharmacology 41:369–376PubMedGoogle Scholar
  111. Malaviya A, Gomes J (2008) Androstenedione production by biotransformation of phytosterols. Bioresour Technol 99:6725–6737PubMedGoogle Scholar
  112. Mamoh L (1937) United States Patent 2, 186, 9006Google Scholar
  113. Manosroia J, Saowakhonb S, Manosroia A (2007) A novel one-step biotransformation of cortexolone-21-acetate to hydrocortisone acetate using Cunninghamella blakesleeana ATCC 8688a. Enzyme Microb Technol 41:322–325Google Scholar
  114. Margot P, Huggenberger F, Amrein J, Weiss B (1998) CGA 279202: a new broad-spectrum strobilurin fungicide. In: Proc Brighton Crop Protect Conf: Pests and Diseases. British Crop Protection Council, Farnham, UK, pp 375–382Google Scholar
  115. Markowski M, Ungeheuer M, Bitran D, Locurto C (2001) Memory enhancing effect of DHEAS in aged mice on a win-shaft water escape task. Physiol Behav 72:521–525PubMedGoogle Scholar
  116. Mehlhom H (1988) Parasitology in focus, facts and trends. Springer, New YorkGoogle Scholar
  117. Meinke PT, Colletti SL, Fisher MH, Wyvratt MJ, Shih TL, Ayer MB, Li C, Lim J, Ok D, Salva S, Warmke LM, Zakson M, Michael BF, deMontigny P, Ostlind DA, Fink D, Drag M, Schmatz DM, Shoop WL (2009) Discovery of the development candidate N-tert-butyl nodulisporamide: a safe and efficacious once monthly oral agent for the control of fleas and ticks on companion animals. J Med Chem 52:3505–3515PubMedGoogle Scholar
  118. Mellon SH, Griffin LD (2002) Neurosteroids: biochemistry and clinical significance. Trends Endocrinol Metab 13:35–43PubMedGoogle Scholar
  119. Miles RS, Moyes A (1978) Comparison of susceptibility of Neisseria meningitidis to sodium sulphadiazine and sodium fusidate in vitro. J Clin Pathol 31:355–358PubMedGoogle Scholar
  120. Moisan H, Pruneau M, Malouin F (2010) Binding of ceftaroline to penicillin-binding proteins of Staphylococcus aureus and Streptococcus pneumoniae. J Antimicrob Chemother 65:713–716PubMedGoogle Scholar
  121. Morris MI, Villmann M (2006a) Echinocandins in the management of invasive fungal infections, part 1. Am J Health Syst Pharm 63:1693–1703PubMedGoogle Scholar
  122. Morris MI, Villmann M (2006b) Echinocandins in the management of invasive fungal infections, Part 2. Am J Health Syst Pharm 63:1813–1820PubMedGoogle Scholar
  123. Mostafa ME, Zohri AA (2000) Progesterone side-chain degradation by some species of Aspergillus flavus group. Folia Microbiol 45:243–247Google Scholar
  124. Mott JL, Zhang D, Freeman JC, Mikolajczak P, Chang SW, Zassenhaus HP (2004) Cardiac disease due to random mitochondrial DNA mutations is prevented by cyclosporin A. Biochem Biophys Res Commun 319:1210–1215PubMedGoogle Scholar
  125. Murray HC, Peterson DH (1952) United States Patent 2602769Google Scholar
  126. Nara F, Tanaka M, Hosoya T, Suzuki-Konagai K, Ogita T (1999a) Scyphostatin, a neutral sphingomyelinase inhibitor from a discomycete, Trichopeziza mollissima: taxonomy of the producing organism, fermentation, isolation, and physico-chemical properties. J Antibiot 52:525–530PubMedGoogle Scholar
  127. Nara F, Tanaka M, Masuda-Inoue S, Yamasato Y, Doi-Yoshioka H, Suzuki-Konagai K, Kumakura S, Ogita T (1999b) Biological activities of scyphostatin, a neutral sphingomyelinase inhibitor from a discomycete, Trichopeziza mollissima. J Antibiot 52:531–535PubMedGoogle Scholar
  128. Negishi S, Cai-Huang Z, Hasumi K, Murakawa S, Endo A (1986) Productivity of molacolin K (mevilonin) in the genus Monascus. Hakko Kogaku Kaishi 64:509–512Google Scholar
  129. Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70:461–477PubMedGoogle Scholar
  130. Newton GGF, Abraham EP (1955) Cephalosporin C, a new antibiotic containing sulphur and D-α-aminoadipic acid. Nature 175:548PubMedGoogle Scholar
  131. Nishitoba T, Sato H, Shirasu S, Sakamura S (1987) Novel triterpenoids from the mycelial mat at the previous stage of fruiting of G. lucidum. Agric Biol Chem 51:619–622Google Scholar
  132. Nissen S, Nicholls S, Sipahi I, Libby P, Raichlen J, Ballantyne C, Davignon J, Erbel R, Fruchart J, Tardif J, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu E (2006) Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. J Am Med Assoc 295:1556–1565Google Scholar
  133. Ondeyka JG, Helms GL, Hensens OD, Goetz MA, Zink DL, Tsipouras A, Shoop WL, Slayton L, Dombrowski AW, Polishook JD, Ostlind DA, Tsou NN, Ball RG, Singh SB (1997) Nodulisporic acid A, a novel and potent insecticide from a Nodulisporium sp. isolation, structure determination, and chemical transformations. J Am Chem Soc 119:8809–8816Google Scholar
  134. Osbourn AE, Lanzotti V (2009) Plant-derived natural products: synthesis, function, and application. Springer, New YorkGoogle Scholar
  135. Otaka T, Kaji A (1973) Evidence that fusidic acid inhibits the binding of aminoacyl-tRNA to the donor as well as the acceptor site of the ribosomes. Eur J Biochem 38:46–53PubMedGoogle Scholar
  136. Panda D, Rathinasamy K, Santra MK, Wilson L (2005) Kinetic suppression of microtubule dynamic instability by griseofulvin: implications for its possible use in the treatment of cancer. PNAS 102:9878–9883PubMedGoogle Scholar
  137. Paz Z, Komon-Zelazowska M, Druzhinina IS, Aveskamp MM, Shnaiderman A, Aluma Y, Carmeli S, Ilan M, Yarden O (2010) Diversity and potential antifungal properties of fungi associated with a Mediterranean sponge. Fungal Divers 42:17–26Google Scholar
  138. Penman R (1962) Fusidic acid in bacterial endocarditis. Lancet 280:1277–1278Google Scholar
  139. Petrič S, Hakki T, Bernhardt R, Zigon D, Crešnar B (2010) Discovery of a steroid 11α-hydroxylase from Rhizopus oryzae and its biotechnological application. J Biotechnol 150:428–437PubMedGoogle Scholar
  140. Pimentel MR, Molina G, Dionísio AP, Maróstica Junior MR, Pastore GM (2011) The use of endophytes to obtain bioactive compounds and their application in biotransformation process. Biotechnol Res Int, Article ID: 576286, doi:10.4061/2011/576286
  141. Pohold DJ, Saravolatz LD, Somerville MM (1987) In vitro susceptibility of gram-positive cocci to LY146032, teicoplanin, sodium fusidate, vancomycin, and rifampicin. J Antimicrob Chemother 20:197–202Google Scholar
  142. Poucheretpet P, Fons F, Rapior S (2006) Biological and pharmacological activity of higher fungi: 20-year retrospective analysis. Cryptogamie Mycol 27:311–333Google Scholar
  143. Pritchard DI (2005) Sourcing a chemical succession for cyclosporin from parasites and human pathogens. Drug Discov Today 10:688–691PubMedGoogle Scholar
  144. Rateb ME, Ebel R (2011) Secondary metabolites of fungi from marine habitats. Nat Prod Rep 28:290–344PubMedGoogle Scholar
  145. Ravn HO (1967) Fucidin og novobiocin som kombinationsbehandling ved akut osteomyelitis og ostitis. Ugeskr Laeger 129:15Google Scholar
  146. Rebacz B, Larsen TO, Clausen MH, Rønnest MH, Löffler H, Ho AD, Krämer A (2007) Identification of griseofulvin as an inhibitor of centrosomal clustering in a phenotype-based screen. Cancer Res 67:6342–6350PubMedGoogle Scholar
  147. Reeves DS (1987) The pharmacokinetics of fusidic acid. J Antimicrob Chemother 20:467–476PubMedGoogle Scholar
  148. Richardson MD, Warnock DW (2003) Fungal infection: diagnosis and management, 3rd edn. Blackwell Publishing Ltd, Oxford, pp 70–72Google Scholar
  149. Robel P, Baulieu E-E (1995) Dehydroepiandrosterone (DHEA) is a neuroactive neurosteroid. Ann NY Acad Sci 774:82–110PubMedGoogle Scholar
  150. Runcie KA, Taylor RJK (2001) A short and efficient route to novel scyphostatin analogues. Org Lett 3:3237–3239PubMedGoogle Scholar
  151. Rupprecht R, Holsboer F (1999) Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci 22:410–416PubMedGoogle Scholar
  152. Saito S, Tanaka N, Fujimoto K, Kogen H (2000) Absolute configuration of scyphostatin. Org Lett 2:505–506PubMedGoogle Scholar
  153. Sallam LAR, El-Refai AM, El-Minofi HA (2005) Physiological and biochemical improvement of the enzyme side-chain degradation of cholesterol by Fusarium solani. Process Biochem 40:203–206Google Scholar
  154. Samanta TB, Ghosh DK (1987) Characterization of progesterone 11 alpha-hydroxylase of Aspergillus ochraceus TS: a cytochrome P-450 linked monooxygenase. J Steroid Biochem 28:327–332PubMedGoogle Scholar
  155. Sasaki T, Takagi M, Yaguchi T, Miyadoh S, Okada T, Koyama M (1992) A new anthelmintic cyclodepsipeptide, PF1022A. J Antibiot 45:692–697PubMedGoogle Scholar
  156. Sauter H, Steglich W, Anke T (1999) Strobilurins: evolution of new class of active substances. Angew Chem Int Ed 38:1328–1349Google Scholar
  157. Scherkenbeck J, Harder A, Plant A, Dyker H (1998) PF1022A—a novel anthelmintic cyclooctadepsipeptide. Modification and exchange of the N-methyl leucine residues. Bioorg Med Chem Lett 8:1035–1040PubMedGoogle Scholar
  158. Schoeller W (1937) United States Patent 2, 184, 167Google Scholar
  159. Schwartz RE, Giacobbe RA, Boand JA, Monaghan RL (1989) L-671,329, a new antifungal agent. I. Fermentation and isolation. J Antibiot 42:163–167PubMedGoogle Scholar
  160. Sedlaczek L (1988) Biotransformations of steroids. Crit Rev Biotechnol 7:187–236PubMedGoogle Scholar
  161. Shaw LM (1989) Advances in cyclosporine pharmacology, measurement, and therapeutic monitoring. Clin Chem 35:1299–1308PubMedGoogle Scholar
  162. Shida D, Takabe K, Kapitonov D, Milstien S, Spiegel S (2008) Targeting SphK1 as a new strategy against cancer. Curr Drug Targets 9:662–673PubMedGoogle Scholar
  163. Shieh YH, Liu CF, Huang YK, Yang JY, Wu IL, Lin CH, Li SC (2001) Evaluation of the hepatic and renal-protective effects of Ganoderma lucidum in mice. Am J Clin Med 29:501–507Google Scholar
  164. Shkumatov VM, Usova EV, Poljakov YS, Frolova NS, Radyuk VG, Mauersberger S, Chernogolov AA, Honeck H, Schunck WH (2002) Biotransformation of steroids by a recombinant yeast strain expressing bovine cytochrome P-45017α. Biochemistry 67:456–467PubMedGoogle Scholar
  165. Shoop WL, Gregory LM, Zakson-Aiken M, Michael BF, Haines HW, Ondeyka JG, Meinke PT, Schmatz DM (2001) Systemic efficacy of nodulisporic acid against fleas on dogs. J Parasitol 87:419–423PubMedGoogle Scholar
  166. Siev M, Weinberg R, Penman S (1969) The selective interruption of nucleolar RNA synthesis in HELA cells by cordycepin. J Cell Biol 41:510–520PubMedGoogle Scholar
  167. Singh SB, Barrett JF (2006) Empirical antibacterial drug discovery—foundation in natural products. Biochem Pharmacol 71:1006–1015PubMedGoogle Scholar
  168. Smith D, Ryan MJ (2009) Fungal sources for new drug discovery. AccessScience, ©McGraw-Hill Companies,
  169. Sonomoto K, Hoq MMD, Tanaka A, Fukui S (1981) Growth of Curvularia lunata spores into mycelial form with various gels, and steroid 11β-hydroxy1ation by the entrapped mycelia. J Ferment Technol 59:465–469Google Scholar
  170. Spiteller P (2008) Chemical defence strategies of higher fungi. Chem Eur J 14:9100–9110Google Scholar
  171. Staudinger H (1907) Zur Kenntniss der Ketene. Diphenylketen. Justus Liebigs Ann Chem 356:51–123Google Scholar
  172. Stirling J, Goodwin S (1977) Susceptibility Bacteroides fragilis to fusidic acid. J Antimicrob Chemother 3:522–523PubMedGoogle Scholar
  173. Strobel GA (2002) Rainforest endophytes and bioactive products. Crit Rev Biotechnol 22:315–333PubMedGoogle Scholar
  174. Strobel G, Daisy B (2003) Bioprospecting for microbial endophytes and their natural products. Microbiol Mol Biol Rev 67:491–502PubMedGoogle Scholar
  175. Sweetman SC (2009) Cardiovascular drugs. Martindale: the complete drug reference, 36th edn. Pharmaceutical Press, London, pp 1155–1434Google Scholar
  176. Taburet AM, Guibert J, Kitzis MD, Sorensen H, Acar JF, Singlas E (1990) Pharmacokinetics of sodium fusidate after single and repeated infusions and oral administration of a new formulation. J Antimicrob Chemother 25:23–31PubMedGoogle Scholar
  177. Tanaka N, Kinoshita T, Masukawa H (1968) Mechanism of protein synthesis inhibition by fusidic acid and related antibiotics. Biochem Biophys Res Commun 15:278–283Google Scholar
  178. Tanaka M, Nara F, Suzuki-Konagai K, Hosoya T, Ogita T (1997) Structural elucidation of scyphostatin, an inhibitor of membrane-bound neutral sphingomyelinase. J Am Chem Soc 119:7871–7872Google Scholar
  179. Tang YJ, Zhong JJ (2004) Modeling the kinetics of cell growth and ganoderic acid production in liquid static cultures of the medicinal mushroom Ganoderma lucidum. Biochem Eng J 21:259–264Google Scholar
  180. Tang W, Gu T, Zhong JJ (2006) Separation of targeted ganoderic acids from Ganoderma lucidum by reversed phase liquid chromatography with ultraviolet and mass spectrometry detections. Biochem Eng J 32:205–210Google Scholar
  181. Taylor G, Bloor K (1962) Antistaphylococcal activity of fucidin. Lancet 279:935–937Google Scholar
  182. Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP, Ebrahim S (2011) Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev:CD004816Google Scholar
  183. Tidwell TT (2008) Hugo (Ugo) Schiff, Schiff bases, and a century of β-lactam synthesis. Angew Chem Int Edit 47:1016–1020Google Scholar
  184. Verbist L (1990) The antimicrobial activity of fusidic acid. J Antimicrob Chemother 25:1–5PubMedGoogle Scholar
  185. Verza M, Arakawa NS, Lopes NP, Kato MJ, Pupo MT, Said S, Carvalho I (2009) Biotransformation of a tetrahydrofuran lignan by the endophytic fungus Phomopsis sp. J Braz Chem Soc 20:195–200Google Scholar
  186. Viola F, Caputo O, Balliano G, Delprino L, Cattel L (1983) Side chain degradation and microbial reduction of different steroids by Aspergillus auroefulgens. J Steroid Biochem 19:1451–1458PubMedGoogle Scholar
  187. von Benz F, Knusel F, Nuesch J, Treichler H, Voser W, Nyfeler R, Keller-Schierlein W (1974) Echinocandin B, ein neuartiges polipeptide-antibiotikum aus Aspergillus nidulans var. echinatus: Isolierung und Bausteine. Helv Chim Acta 57:2459–2477Google Scholar
  188. von Daehne W, Godtfredsen WO, Rasmussen PR (1979) Structureactivity relationships in fusidic acid-type antibiotics. Adv Appl Microbiol 25:95–146Google Scholar
  189. Von Jagow G, Gribble GW, Trumpower BL (1986) Mucidin and strobilurin A are identical and inhibit electron transfer in the cytochrome bc 1 complex of the mitochondrial respiratory chain at the same site as myxothiazol. Biochemistry 25:775–780Google Scholar
  190. von Samson-Himmelstjerna G, Harder A, Sangster NC, Coles GC (2005) Efficacy of two cyclooctadepsipeptides, PF1022A and emodepside, against anthelmintic-resistant nematodes in sheep and cattle. Parasitology 130:343–347Google Scholar
  191. Waldmeier PC, Zimmermann K, Qian T, Tintelnot-Blomley M, Lemasters JJ (2003) Cyclophilin D as a drug target. Curr Med Chem 10:1485–1506PubMedGoogle Scholar
  192. Walsh C (2003) Antibiotics: actions, origins, resistance. ASM Press, Washington DCGoogle Scholar
  193. Wasser SP (2002) Medicinal mushrooms as a source of antitumor and immunomodulatory polysaccharides. Appl Microbiol Biotechnol 60:258–274PubMedGoogle Scholar
  194. Wasser SP, Weis AL (1999) Therapeutic effects of substances occurring in higher basidiomycetes mushrooms: a modem perspective. Crit Rev Immunol 19:65–96PubMedGoogle Scholar
  195. Waxman DJ, Strominger JL (1983) Penicillin-binding proteins and the mechanism of action of beta-lactam antibiotics. Annu Rev Biochem 52:825–869PubMedGoogle Scholar
  196. Weber W, Anke T, Steffan B, Steglich W (1990) Antibiotics from basidiomycetes. XXXII. Strobilurin E: a new cytostatic and antifungal (E)-beta-methoxyacrylate antibiotic from Crepidotus fulvotomentosus Peck. J Antibiot 43:207–212PubMedGoogle Scholar
  197. Welte T, Pletz MW (2010) Antimicrobial treatment of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) pneumonia: current and future options. Int J Antimicrob Agents 36:391–400PubMedGoogle Scholar
  198. Whelan RS, Kaplinskiy V, Kitsis RN (2010) Cell death in the pathogenesis of heart disease: mechanisms and significance. Annu Rev Physiol 72:19–44PubMedGoogle Scholar
  199. Whitby M (1999) Fusidic acid in septicaemia and endocarditis. Int J Antimicrob Agents 12:S17–S22PubMedGoogle Scholar
  200. Williams DH, Stone MJ, Hauck PR, Rahman SK (1989) Why are secondary metabolites (natural products) biosynthesized? J Nat Prod 52:1189–1208PubMedGoogle Scholar
  201. Williamson J, Russell F, Doig WM, Paterson RW (1970) Estimation of sodium fusidate levels in human serum, aqueous humour, and vitreous body. Br J Ophthalmol 54:126–130PubMedGoogle Scholar
  202. Wise R, Pippard M, Mitchard M (1977) The disposition of sodium fusidate in man. Br J Clin Pharmacol 4:615–619PubMedGoogle Scholar
  203. Xu J, Ebada SS, Proksch P (2010) Pestalotiopsis a highly creative genus: chemistry and bioactivity of secondary metabolites. Fungal Divers 44:15–31Google Scholar
  204. Yamashita M, Katsumata M, Iwashima M, Kimura M, Shimizu C, Kamata T, Shin T, Seki N, Suzuki S, Taniguchi M, Nakayama T (2000) T cell receptor-induced calcineurin activation regulates T helper type 2 cell development by modifying the interleukin 4 receptor signaling complex. J Exp Med 191:1869–1879PubMedGoogle Scholar
  205. Yaskowiak ES, March PE (1995) Small clusters of divergent amino acids surrounding the effector domain mediate the varied phenotypes of EF-G and LepA expression. Mol Microbiol 15:943–953PubMedGoogle Scholar
  206. Yoon SY, Eo SK, Kim YS, Lee CK, Han SS (1994) Antimicrobial activity of Ganoderma lucidum extract alone and in combination with some antibiotics. Arch Pharm Res 17:438–442PubMedGoogle Scholar
  207. Zakharychev VV, Kovalenko LV (1998) Natural compounds of the strobilurin series and their synthetic analogues as cell respiration inhibitors. Russ Chem Rev 67:535–544Google Scholar
  208. Zeelen FJ (1990) Medicinal chemistry of steroids. Elsevier, AmsterdamGoogle Scholar
  209. Zhang HW, Song YC, Tan RX (2006) Biology and chemistry of endophytes. Nat Prod Rep 23:753–771PubMedGoogle Scholar
  210. Zinner SH, Lagast H, Klastersky J (1981) Antistaphylococcal activity of rifampin with other antibiotics. J Infect Dis 144:365–371PubMedGoogle Scholar

Copyright information

© Kevin D. Hyde 2011

Authors and Affiliations

  1. 1.Heinrich-Heine-Universität Düsseldorf, Institut für Pharmazeutische Biologie und BiotechnologieDüsseldorfGermany

Personalised recommendations