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Potential Pharmaceuticals from Insects and Their Co-Occurring Microorganisms

  • Konrad DettnerEmail author
Part of the Biologically-Inspired Systems book series (BISY, volume 2)

Abstract

Because of their enormous species diversity insects represent an interesting and promising source for low molecular biologically active natural products which either are de novo synthesized by the insect or by associated microorganisms. Many of the structures show that potential pharmaceuticals can be found which may be used for human and veterinary medicine. Concerning the toxic terpene anhydride cantharidin it is demonstrated that synthetically obtained low toxic analogues may be suitable for use as pharmaceuticals or in other contexts. In addition low molecular compounds from insect-derived microorganisms are compiled according to the taxonomy, this means the order of the host insects as far as these compounds are of pharmaceutical interest. Remarkably various compounds have also been described from other non-insect sources. It is shown that only a few natural products, such as pederin, result from a true symbiotic interaction between host insect and bacteria. In most other cases the presented metabolites from insect-derived microorganisms are produced in the lab and it has to be clarified whether they are even produced within the host insect.

Keywords

Secondary compounds Cantharidin Insect-symbionts Symbiotic fungi and bacteria Insects Bioprospecting Pharmaceuticals 

Notes

Acknowledgments

The help of E. Helldörfer (Bayreuth) and S. Wagner (Bayreuth) in preparing the manuscript is gratefully acknowledged. Moreover, I am thankful to W. Boland (Jena), H. P. Fiedler (Tübingen), W. Francke (Hamburg), K. Gebhardt. (Tübingen), H. G. Kallenborn (Saarbrücken), P. Krastel (Göttingen), J. Rheinheimer (Ludwigshafen), A. Zeeck (Göttingen) for fruitful cooperation in the field of insect microorganisms and chemical analysis. Finally, I especially thank A. Vilcinskas (Gießen) for fruitful discussions and his help. Moreover, I am thankful to an anonymous reviewer for improving this manuscript version.

References

  1. Ahn MY, Hahn BS, Lee PJ, Wu SJ, Kim SY (2006) Purification and Characterization of Anticoagulant Protein from the Tabanus, Tabanus bivittatus. Arch Pharm Res 29:418–423PubMedGoogle Scholar
  2. Ahn MY, Ryu KS, Lee YW, Kim YS (2000) Cytotoxicity and L-Amino Acid Oxidase Activity of Crude Insect Drugs. Arch Pharm Res 23:477–481PubMedGoogle Scholar
  3. Altincicek B, Vilcinskas A (2007) Analysis of the immune-inducible transcriptome from microbial stress resistant, rat-tailed maggots of the drone fly Eristalis tenax. BMC Genomics 8:326–338PubMedGoogle Scholar
  4. Altincicek B, Vilcinskas A (2009) Septic injury-inducible genes in medicinal maggots of the green blow fly Lucilia sericata. Ins Mol Biol 18:119–125Google Scholar
  5. Azumi M, Ishidoh K, Kinoshita H, Nihira T, Ihara F, Fujita T, Igarashi Y (2008) Aurovertins F-H from the Entomopathogenic Fungus Metarhizium anisopliae. J Nat Prod 71:278–280PubMedGoogle Scholar
  6. Bangera MG, Thomashow LS (1999) Identification and Characterization of a Gene Cluster for Synthesis of the Polyketide Antibiotic 2,4-Diacetylphloroglucinol from Pseudomonas fluorescens Q2-87. J Bacteriol 181:3155–3163Google Scholar
  7. Baumann P, Moran NA, Baumann L (2006) Bacteriocyte-associated endosymbionts of insects. Prokaryotes 1:403–438Google Scholar
  8. Bengoa Vallejo RB, de Iglesias MEL, Gómez-Martín B, Gómez RS, Crespo AS (2008) Application of Cantharidin and Podophyllotoxin for the Treatment of Plantar Warts. J Am Podiatr Med Assoc 98:445–450Google Scholar
  9. Bergan T (1975) Epidemiological typing of Pseudomonas aeruginosa. In: MRW Brown (ed) Resistance of Pseudomonas aeruginosa. Wiley, London, 189–235Google Scholar
  10. Blum MS (1981) Chemical defences of arthropods. Academic Press, New York, NYGoogle Scholar
  11. Bobylev MM, Bobyleva LI, Cutler HG, Cutler SJ, Strobel GA (2000) Effects of Synthetic Congeners of the Natural Product Phytotoxins Maculosins-1 and -2 on Growth of Wheat Coleoptile (Triticum aestivum L. cv. Wakeland). In: NR Spencer (ed) Proceedings of the X International Symposium on Biological Control of Weeds 4–14 July 1999, Montana State University, Bozeman, Montana, USA. 209–214Google Scholar
  12. Bochis RJ, Fisher MH (1968) The structure of Palasonin. Tetrahedron Lett 16:1971–1974Google Scholar
  13. Bourtzis K, Miller TA (2003) Insect Symbiosis. CRC, Boca Raton, FLGoogle Scholar
  14. Bourtzis K, Miller TA (2006) Insect Symbiosis, vol 2. CRC, Boca Raton, FLGoogle Scholar
  15. Bourtzis K, Miller TA (2009) Insect Symbiosis, vol 3. CRC, Boca Raton, FLGoogle Scholar
  16. Bringmann G, Noll TF, Gulder TAM, Grüne M, Dreyer M, Wilde C, Pankewitz F, Hilker M, Payne GD, Jones AL, Goodfellow M, Fiedler HP (2006) Different polyketide folding modes converge to an identical molecular architecture. Nat Chem Biol 2:429–433PubMedGoogle Scholar
  17. Buchner P (1953) Endosymbiose der Tiere mit pflanzlichen Mikroorganismen. Birkhäuser, BaselGoogle Scholar
  18. Cane DE (1999) Sesquiterpene Biosynthesis: Cyclization Mechanisms. In: (DE Cane, ed.) Comprehensive Natural Products Chemistry, vol 2. Elsevier, Amsterdam, 155–200Google Scholar
  19. Chang C, Liu D, Lin S, Liang H, Hou W, Huang W, Chang C, Ho F, Liang Y (2008) Liposome encapsulation reduces cantharidin toxicity. Food Chem Toxicol 46:3116–3121PubMedGoogle Scholar
  20. Chernysh S, Kim SI, Bekker G, Pleskach VA, Filatova NA, Anikin VB, Plantonov VG, Bulet P (2002) Antiviral and antitumor peptides from insects. PNAS 99:12628–12632PubMedGoogle Scholar
  21. Coloe J, Burkhart CN, Morrell DS (2009) Molluscum Contagiosum: Whats new and true? Pediatr Ann 38:321–325PubMedGoogle Scholar
  22. Coloe J, Morrell DS (2009) Cantharidin Use Among Pediatric Dermatologists in the Treatment of Molluscum Contagiosum. Pediatr Dermatol 26:405–408PubMedGoogle Scholar
  23. Costa-Neto EM (2005) Entomotherapy, or the medicinal use of insects. J Ethnobiol 25:93–114Google Scholar
  24. Cutler HG (1975) Cantharidin: Novel effects on plants, Plant & Cell. Physiol 16:181–184Google Scholar
  25. Dale C, Moran NA (2006) Molecular Interactions between Bacterial Symbionts and Their Hosts. Cell 126:453–465PubMedGoogle Scholar
  26. Daly JW, Garraffo HM, Spande TF (1999) Alkaloids from Amphibian Skins. In: SW Pelletier, (ed) Alkaloids: Chemical & Biological Perspectives. Pergamon, New York, NY, 1–159Google Scholar
  27. Dettner K (1997) Inter- and Intraspecific Transfer of Toxic Insect Compound Cantharidin. In: K Dettner, G Bauer, W Völkl, (eds) Vertical Food Web Interactions. Ecological Studies 130. Springer, Berlin, 115–145Google Scholar
  28. Dettner K (2003) Insekten und Mikroorganismen. In: K Dettner, W Peters, (eds) Lehrbuch der Entomologie, 2 Aufl. Spektrum, Heidelberg, 613–633Google Scholar
  29. Dettner K (2007) Gifte und Pharmaka aus Insekten – ihre Herkunft, Wirkung und ökologische Bedeutung. Entomologie heute 19:3–28Google Scholar
  30. Dettner K (2010) Chemical defense and toxins of lower terrestrial and freshwater animals. In: L. Mander, HW. Lui, (eds) Comprehensive Natural Products II Chemistry and Biology, Volume 4. Elsevier, Oxford, 387–410Google Scholar
  31. Dettner K, Bauer G, Völkl W (1997) Evolutionary patterns and driving forces in vertical food web interactions. In: K. Dettner, G. Bauer, W. Völkl (eds) Vertical Food Web Interactions. Ecological Studies 130. Springer, Berlin, 337–377Google Scholar
  32. Dettner K, Peters W (2003) Lehrbuch der Entomologie, 2nd edn. Spektrum, HeidelbergGoogle Scholar
  33. Dettner K, Schramm S, Seidl V, Klemm K, Gäde G, Fietz O, Boland W (2003) Occurrence of terpene anhydride Palasonin and Palasoninimide in blister beetle Hycleus lunata (Coeloptera: Meloidae). Biochem Syst Ecol 31:203–205Google Scholar
  34. Dowd PF (1992) Insect fungal symbionts: a promising source of detoxifying enzymes. J Ind Microbiol 9:149–161Google Scholar
  35. Dumbacher JP, Wako A, Derrickson SR, Samuelson A, Spande TF, Daly JW (2004) Melyrid beetles (Choresine): a putative source for the batrachotoxin alkaloids found in poison-dart frogs and toxic passerine birds. PNAS 101:15857–15860PubMedGoogle Scholar
  36. Dunn AK, Stabb EV (2005) Culture-Independent Characterization of the Microbiota of the Ant Lion Myrmeleon mobilis (Neuroptera: Myrmeleontidae). Appl Environ Microbiol 71:8784–8794PubMedGoogle Scholar
  37. Durmazlar SPK, Atacan D, Eskioglu F (2009) Cantharidin treatment for recalcitrant facial flat warts: A preliminary study. J Dermatol Treat 20:114–119Google Scholar
  38. Eisner T (2003) For love of insects. Belknap Press, Cambridge, MAGoogle Scholar
  39. Eisner T, Eisner M, Siegler M (2005) Secret weapons, 2nd ed. Belknap Press, Cambridge, MAGoogle Scholar
  40. Erental A, Harel A, Yarden O (2007) Type 2A Phosphoprotein Phosphatase Is Required for a sexual Development and Pathogenesis of Sclerotinia sclerotiorum. MPMI 20:944–954PubMedGoogle Scholar
  41. Eyal J, Mabud A, Fischbein KL, Walter JF, Osborne LS, Landa Z (1994) Assessment of Beauveria bassiana Nov. EO-1 Strain, Which Produces a Red Pigment for Microbial Control. Appl Biochem Biotechnol 44:65–80Google Scholar
  42. Fietz O, Dettner K, Görls H, Klemm K, Boland W (2002) (R)-(+)-Palasonin, A Cantharidin-Related Plant Toxin, also occurs in Insect Hemolymph and Tissues. J Chem Ecol 28:1315–1327PubMedGoogle Scholar
  43. Fleischmann W, Grassberger M, Sherman R (2004) Maggot Therapy. Thieme, StuttgartGoogle Scholar
  44. Fortenbach CR, Modjahedi BS, Maibach HI (2008) Role of Physical Chemical Properties in Drug Relay into Skin Compartments. Skin Pharmacol Physiol 21:294–299PubMedGoogle Scholar
  45. Francke W, Dettner K (2005) Chemical signalling in Beetles. In: Topics in Current Chemistry 240. Springer, Heidelberg, 85–166Google Scholar
  46. Fredenhagen A, Tamura SY, Kenny PTM, Komura H, Naya Y, Nakanishi K, Nishiyama K, Sugiura M, Kita H (1987) Andrimid, a New Peptide Antibiotic Produced by an Intracellular Bacterial Symbiont Isolated from a Brown Planthopper. J Am Chem Soc 109:4409–4411Google Scholar
  47. Freiberg C (2005) Entdeckung von Inhibitoren der bakteriellen Acetyl-CoenzymA-Carboxylase mit antibiotischer Aktivität. Biospektrum 2:180–182Google Scholar
  48. Freiberg C, Brunner NA, Schiffer G, Lampe T, Pohlmann J, Brands M, Raabe M, Häbich D, Ziegelbauer K (2004) Identification and Characterization of the First Class of Potent Bacterial Aceyl-CoA Carboxylase Inhibitors with Antibacterial Activity. J Biol Chem 279: 26066–26073PubMedGoogle Scholar
  49. Fryer RI, Boris A, Earley JV, Reeder E (1977) 2-(2-Aminoethylamino)-l,2-diphenylethanol Derivatives, a New Class of Topical Antiinflammatory Agents. J Med Chem 20:1268–1272PubMedGoogle Scholar
  50. Fugmann B, Lang-Fugmann S, Steglich W(H) (1996–1999) Römpp Lexikon Naturstoffe, Band 1–6. Thieme, StuttgartGoogle Scholar
  51. Gebhardt K, Schimana J, Krastel P, Dettner K, Rheinheimer J, Zeeck A, Fiedler H-P (2002) Endophenazines A – D, New Phenazine Antibiotics from the Arthropod Associated Endosymbiont Streptomyces anulatus. I. Taxonomy, Fermentation, Isolation and Biological Activities. J Antibiot 55(9):794–800PubMedGoogle Scholar
  52. Grabley S, Thiericke R (2000) Drug discovery from nature, 2nd edn. Springer, BerlinGoogle Scholar
  53. Graziano MJ, Pessah IN, Matsuzawa M, Casina JE (1988) Partial Characterization of Specific Cantharidin Binding Sites in Mouse Tissues. Mol Pharmacol 33:706–712PubMedGoogle Scholar
  54. Guha PK, Poi R, Bhattacharyya A (1990) An Imide from the Pods of Butea monosperma. Phytochemistry 29:2017Google Scholar
  55. Haeder S, Wirth R, Herz H, Spiteller D (2009) Candicidin-producing Streptomyces support leaf-cutting ants to protect their fungus garden against the pathogenic fungus Escovopsis. PNAS 106:4742–4746PubMedGoogle Scholar
  56. Hashimoto M, Taguchi T, Nishida S, Ueno K, Koizumi K, Abrada M, Ichinose K (2007) Isolation of 8-Phosphate Ester Derivatives of Amicoumacins: structure-activity Relationship of Hydroxy Amino Acid Moiety. J Antibiot 60:752–756PubMedGoogle Scholar
  57. Helson JE, Todd LC, Johns T, Aiello A, Windsor DM (2009) Ecological and evolutionary bioprospecting: using aposematic insects as guides to rainforest plants active against disease. Frontiers Ecol Environ/Ecol Soc Am 7:130–134Google Scholar
  58. Hemp C (2001) Ethnozoological research on invertebrates on Mt. Kilimanjaro, Tanzania. Ecotropica 7:139–149Google Scholar
  59. Hemp C, Hemp A, Dettner K (1999) Canthariphilous Insects in east Africa. J East Afr Nat Hist 88:1–15Google Scholar
  60. Hilker M, Eschbach U, Dettner K (1992) Occurrence of Anthraquinones in Eggs and Larvae of Several Galerucinae (Coleoptera: Chrysomelodae). Naturwissenschaften 79:271–274Google Scholar
  61. Hoppe HA (1977) Tierische Drogen. In: Hoppe HA (Hrsg) Drogenkunde, Band 2, 8 Auflage. De Gruyter, Berlin, 247–326Google Scholar
  62. Isaka M, Kittakoop P, Kirtikara K, Hywel-Jones NL, Thebtaranonth Y (2005) Bioactive Substances from Insect Pathogenic Fungi. Acc Chem Res 38:813–823PubMedGoogle Scholar
  63. Itoh J, Omoto S, Nishizawa N, Kodama J, Inouye S (1982) Chemical Structures of Amicoumacins Produced by Bacillus pumilus. Agric Biol Chem 46:2659–2665Google Scholar
  64. Jigami Y, Harada N, Uemura H, Tanaka H, Ishikawa K, Nakasato S, Kita H, Sugiura M (1986) Identification of a polymyxin produced by a symbiontic microorganism isolated from the brown planthopper Nilaparavata lugens. Agric Biol Chem 50:1637–1639Google Scholar
  65. Jørgensen H, Fjærvik E, Hakvåg S, Bruheim P, Bredholt H, Klinkenberg G, Ellingsen TE, Zotchev SB (2009) Candicidin Biosynthesis Gene Cluster Is Widely Distributed among Streptomyces spp. Isolated from the Sediments and the Neuston Layer of the Trondheim Fjord, Norway. Appl Environ Microbiol 75:3296–3303PubMedGoogle Scholar
  66. Kadavy DR, Hornby JM, Harverkost T, Nickerson KW (2000) Natural antibiotic resistance of bacteria isolated from larvae of the oil fly Helaeomyia petrolei. Appl Environ Microbiol 2000:4615–4619Google Scholar
  67. Kaltenpoth M, Goettler W, Dale C, Stubblefield JW, Herzner G, Roeser-Mueller K, Strohm E (2006) Candidatus Streptomyces philanthi, an endosymbiontic streptomycete in the antennae of Philanthus digger wasps. Int J Syst Evol Microbiol 56:1403–1411PubMedGoogle Scholar
  68. Kaltenpoth M, Göttler W, Herzner G, Strohm E (2005) Symbiotic Bacteria Protect Wasp Larvae from Fungal Infestation. Curr Biol 15:475–479PubMedGoogle Scholar
  69. Kato-Noguchi H, Kobayashi K (2009) Jasmonic acid, protein phosphatase inhibitor, metals and UV-irradiation increased momilactone A and B concentrations in the moss Hypnum plumaeforme. J Plant Physiol 166:118–1122Google Scholar
  70. Kellner RLL (2002) Molecular identification of an endosymbiontic bacterium associated with pederin biosynthesis in Paederus sabeus (Coleoptera: Staphylinidae). Insect Biochem Mol Biol 32:389–395PubMedGoogle Scholar
  71. Kellner RLL, Dettner K (1995) Allocation of pederin during life-time of Paederus rove beetles (Coleoptera: Staphylinidae): evidence for polymorphism of hemolymph toxin. J Chem Ecol 21:1719–1733Google Scholar
  72. Kellner RLL, Dettner K (1996) Differential efficacy of toxic pederin in deterring potential arthropod predators of Paederus (Coleoptera: Staphylinidae) offspring. Oecologia 107:293–300Google Scholar
  73. Kenny PTM, Tamura SY, Fredenhagen A, Naya Y, Nakanishi K, Nishiyama K, Sugiura M, Kita H, Komura H (1989) Symbiotic Microorganisms of Insects: a Potential New Source for Biologically Active Substances. Pestic Sci 27:117–131Google Scholar
  74. Kevany BM, Rasko DA, Thomas MG (2009) Characterization of the complete zwittermicin A biosynthesis gene cluster from Bacillus cereus. Appl Environ Microbiol 75:1144–1155PubMedGoogle Scholar
  75. Kirk RE, Othmer DF (1993) Encyclopaedia of Chemical Technology, vol 3. Wiley, New York, NYGoogle Scholar
  76. Kok SHL, Chui CH, Lam WS, Chen J, Lau FY, Wong RSM, Cheng GYM, Lai PBS, Leung TWT, Yu MWY, Tang JCO, Chan ASC (2007) Synthesis and structure evaluation of a novel cantharimide and its cytotoxicity on SK-Hep-1 hepatoma cells. Bioorg Med Chem Lett 17:1155–1159PubMedGoogle Scholar
  77. König H, Varma A (2006) Intestinal microorganisms of termites and other invertebrates. Springer, BerlinGoogle Scholar
  78. Kost C, Lakatos T, Böttcher I, Arendholz W-R, Redenbach M, Wirth R (2007) Non-specific associations between filamentous bacteria and fungus-growing ants. Naturwissenschaften 94:821–828PubMedGoogle Scholar
  79. Laurent P, Braekman JC, Daloze D (2005) Insect Chemical defense. In: Topics in Current Chemistry 240. Springer, Heidelberg, 167–230Google Scholar
  80. Lee JC, Coval SJ, Clardy J (1996) A cholesteryl ester transfer protein inhibitor from an insect-associated fungus. J Antibiot 49:693–696PubMedGoogle Scholar
  81. Lehane MJ (2005) Biology of blood-sucking insects. Cambridge University Press, Cambridge, MAGoogle Scholar
  82. Li YM, Casida JE (1992) Cantharidin-binding protein: Identification as protein phosphatase 2A. Proc Natl Acad Sci USA 89:11867–11870PubMedGoogle Scholar
  83. Liu XH, Blazsek I, Comisso M, Legras S, Quittet P, Anjo A, Wang GS, Misset JL (1995) Effects of Norcantharidin, a Protein Phosphatase Type-2A Inhibitor, on the Growth of Normal and Malignant Haemopoietic Cells. Eur J Cancer 31A:953–963PubMedGoogle Scholar
  84. Liu X, Fortin PD, Walsh CT (2008) Andrimid producers encode an acetyl-CoA carboxyltransferase subunit resistant to the action of the antibiotic. PNAS 105:13321–13326PubMedGoogle Scholar
  85. Mahmud T, Flatt PM, Wu X (2007) Biosynthesis of Unusual Aminocyclitol-Containing Natural Products. J Nat Prod 70:1384–1391PubMedGoogle Scholar
  86. Mateo N, Nader W, Tamayo G (2001) Bioprospecting. In: Levin SA (ed) Encyclopedia of Biodiversity, vol 1. Academic Press, New York, NY, 471–487Google Scholar
  87. Matsuzawa M, Graziano MJ, Casida JE (1987) Endothal and Cantharidin Analogues: Relation of Structure to Herbicidal Activity and Mammalian Toxicity. J Agric Food Chem 35:823–829Google Scholar
  88. McCormick J, Carrel J (1987) Cantharidin Biosynthesis and Function in Meloid Beetles. In: G Prestwich, G Blomquist (eds) Pheromone Biochemistry. Academic Press Inc., Orlando, FL, 207–350Google Scholar
  89. Mebs D, Pogoda W, Schneider M, Kauert G (2009) Cantharidin and demethylcantharidin (palasonin) content of blister beetles (Coleoptera: Meloidae) from southern Africa. Toxicon 53:466–468PubMedGoogle Scholar
  90. Moed L, Tor SA, Chang MW (2001) Cantharidin Revisited – A Blistering Defence of an Ancient Medicine. Arch Dermatol 137:1357–1360PubMedGoogle Scholar
  91. Moran NA, McCutcheon JP, Nakabachi A (2008) Genomics and Evolution of Heritable Bacterial Symbionts. Ann Rev Genet 42:165–190PubMedGoogle Scholar
  92. Morgan ED (2004) Biosynthesis in Insects. Royal Society of Chemistry, Cambridge, MAGoogle Scholar
  93. Morris T, Stables M, Hobbs A, de Souza P, Colville-Nash P, Warner T, Newson J, Bellingan G, Gilroy DW (2009) Effects of Low-Dose Aspirin on Acute Inflammatory Responses in Humans. J Immunol 183:2089–2996PubMedGoogle Scholar
  94. Nagaoka T, Nakata K, Kouno K, Ando T (2004) Antifungal activity from an antagonistic fungus against Phytophthora infestans. Z Naturforsch 59c:302–304Google Scholar
  95. Nakatini T, Konishi T, Miyahara K, Noda N (2004) Three Novel Cantharidin-Related Compounds from the Chinese Blister Beetle, Mylabris phalerata Pall. Chem Pharm Bull 56:807–809Google Scholar
  96. Narquizian R, Kocienski PJ (2000) The Pederin Family of Antitumor Agents: Structures, Synthesis and Biological Activity. In: J Mulzer, R Bohlmann eds The Roe of Natural Products in Drug Discovery. Springer, Berlin, 25–55Google Scholar
  97. Needham J, Kelly MT, Ishige M, Andersen RJ (1994) Andrimid and Moiramides A-C, Metabolites Produced in Culture by a Marine Isolate of the Bacterium Pseudomonas fluorescens: Structure Elucidation and Biosynthesis. J Org Chem 59:2058–2063Google Scholar
  98. Newman DJ, Cragg MG (2007) Natural Products as Sources of New Drugs over the last 25 years. J Nat Prod 70:461–477PubMedGoogle Scholar
  99. Nikbakhtzadeh MR, Dettner K, Boland W, Göde G, Dötterl S (2007) Intraspecific transfer of cantharidin within selected members of the family Meloidae (Insecta: Coleoptera). J Insect Physiol 53:890–899PubMedGoogle Scholar
  100. Nikbakhtzadeh MR, Ebramihi B (2007) Detection of cantharidin-related compounds in Mylabris impressa (Coleoptera: Meloidae). J Venom Anim Toxins Incl Trop Dis 13:1–6Google Scholar
  101. Nishiwaki H, Ito K, Otsuki K, Yamamoto H, Komai K, Matsuda K (2004) Purification and functional characterization of insecticidal sphingomyelinase C produced by Bacillus cereus. Eur J Biochem 271:601–606PubMedGoogle Scholar
  102. Oclarit JM (1997) Andrimid, an antimicrobial substance produced by Vibrio sp. bacterium associated within the marine sponge Hyatella sp. Mindanao Forum 12(2):165–171Google Scholar
  103. Oh D-C, Poulsen M, Currie CR, Clardy J (2009a) Dentigerumycin: a bacterial mediator of an ant-fungus symbiosis. Nat Chem Biol 5:391–393PubMedGoogle Scholar
  104. Oh D-C, Scott JJ, Currie CR, Clardy J (2009b) Mycangimycin, a Polyene Peroxide from a Mutualist Streptomyces sp. Org Lett 11:633–636PubMedGoogle Scholar
  105. Opitz SEW, Müller C (2009) Plant chemistry and insect sequestration. Chemoecology 19:117–154Google Scholar
  106. Pankewitz F, Zöllmer A, Gräser Y, Hilker M (2007a) Anthraquinones as Defensive Compounds in Eggs of Galerucini Leaf Beetles: Biosynthesis by the Beetles? Arch Insect Biochem Physiol 66:98–108PubMedGoogle Scholar
  107. Pankewitz F, Zöllmer A, Hilker M, Gräser Y (2007b) Presence of Wolbachia in Insect Eggs Containing Antimicrobially Active Anthraquinones. Microbial Ecol 54:713–721Google Scholar
  108. Paterson RR (2008) Cordyceps: a traditional Chinese medicine and another fungal therapeutic biofactory? Phytochemistry 69:1469–1495PubMedGoogle Scholar
  109. Pemberton RW (1999) Insects and other arthropods used as drugs in Korean traditional medicine. J Ethnopharmacol 65:207–216PubMedGoogle Scholar
  110. Piel J (2002) A polyketide synthase-peptide synthetase gene cluster from an uncultured bacterial symbiont of Paederus beetles. PNAS 99:14002–14007PubMedGoogle Scholar
  111. Piel J (2004) Metabolites from symbiotic bacteria. Nat Prod Rep 21:519–538PubMedGoogle Scholar
  112. Piel J (2009) Metabolites from symbiotic bacteria. Nat Prod Rep 26:338–362PubMedGoogle Scholar
  113. Piel J, Höfer I, Hui D (2004) Evidence for a Symbiosis Island Involved in Horizontal Acquisition of Pederin Biosynthetic Capabilities by the Bacterial Symbiont of Paederus fuscipes Beetles. J Bacteriol 186:1280–1286PubMedGoogle Scholar
  114. Pietra F (2002) Biodiversity and Natural Product Diversity. In: Tetrahedron Organic Chemistry Series. Pergamon, Amsterdam, 1–347Google Scholar
  115. Pontes MH, Dale C (2006) Culture and manipulation of insect facultative symbionts. Trends Microbiol 14:406–412PubMedGoogle Scholar
  116. Reithofer MR, Valiahdi SM, Galanski M, Jakupec MA, Arion VB, Keppler BK (2008) Novel Endothall-Containing Platinum (IV) Complexes: Synthesis, Characterization, and Cytotoxic Activity. Chem Biodivers 5:2160–2170PubMedGoogle Scholar
  117. Romero MR, Serrano MA, Efferth T, Alvarez M, Marin JJ (2007) Effect of Cantharidin, Cephalotaxine and Homoharringtonine on “in vitro” Models of Hepatitis B Virus (HBV) and Bovine Viral Diarhoea Virus (BVDV) Replication. Planta Med 73:552–558PubMedGoogle Scholar
  118. Santos AV, Dillon RJ, Dillon VM, Reynolds SE, Samuels RI (2004) Occurrence of the antibiotic producing bacterium Burkholderia sp. in colonies of the leaf-cutting ant Atta sextens rubropilosa. FEMS Microbiol Lett 239:319–323PubMedGoogle Scholar
  119. Schlörke O, Krastel P, Müller I, Usón I (2002) Structure and Biosynthesis of Cetoniacytone A, a Cytotoxic Aminocarba Sugar Produced by an Endosymbiontic Actinomyces. J Antibiot 55(7):635–642PubMedGoogle Scholar
  120. Schweppe H (1993) Handbuch der Naturfarbstoffe. Nikol, HamburgGoogle Scholar
  121. Scott JJ, Oh DC, Yuceer MC, Klepzig KD, Clardy J, Currie CR (2008) Bacterial protection of beetle-fungus mutualism. Science 322:63PubMedGoogle Scholar
  122. Shan H, Cai Y, Liu Y, Zeng W, Chen H, Fan B, Liu X, Xu Z, Wang B, Xian L (2006) Cytotoxicity of cantharidin analogues targeting protein phosphatase 2A. Anticancer Drugs 17:905–911PubMedGoogle Scholar
  123. Sikorski JA (2006) Cholesteryl ester transfer protein inhibitors as potential new therapies for coronary artery disease. Expert Opin Ther Pat 16:753–772Google Scholar
  124. Singh MP, Mroczenski-Wildey MJ, Steinberg DA, Andersen RJ, Maiese WM, Greenstein M (1997) Biological Activity and Mechanistic Studies of Andrimid. J Antibiot 50:270–273Google Scholar
  125. Steglich W, Fugmann B, Lang-Fugmann S (1997) Römpp Lexikon Naturstoffe. Thieme, StuttgartGoogle Scholar
  126. Stierle AC, Cardellina JH, Strobel GA (1988) Maculosin, a host specific phytotoxin for spotted knapweed from Alternaria alternate. Proc Natl Acad Sci USA 85:8008–8011PubMedGoogle Scholar
  127. Suguira M, Maohara K, Nara E, Kaji T, Koyama T, Mori T (1992) Manufacture of herbicide MBH-001 with microorganisms. Jpn Kokai Tokkyo Koho, Patent no JP 04342576, 6 ppGoogle Scholar
  128. Sukumar P, Edwards KS, Rahman A, DeLong A, Muday GK (2009) PINOID Kinase Regulates Root Gravitropism through Modulation of PIN2-Dependent Basipetal Auxin Transport in Arabidopsis. Plant Physiol 150:722–735PubMedGoogle Scholar
  129. Sun W, Zhang Y-Q, Huang Y, Zhang Y-Q, Yang ZY, Liu Z-H (2009) Nocardia jinanensis sp. nov., an amicoumacin B-producing actinomycete. Int J Syst Evol Microbiol 59:417–420PubMedGoogle Scholar
  130. Thongtan J, Saenboonrueng J, Rachtawee P, Isaka M (2006) An Antimalarial Tetrapeptide from the Entomopathogenic Fungus Hirsutella sp. BCC 1528. J Nat Prod 69:713–714PubMedGoogle Scholar
  131. Ullmann (2003) Ullmanns Encyclopedia of Industrial Chemistry, vol 3, 6th rev edn. Wiley-VCH, WeinheimGoogle Scholar
  132. Vilcinskas A, Gross J (2005) Drugs from bugs: the use of insects as a valuable source of transgenes with potential in modern plant protection strategies. J Pest Sci 78:187–191Google Scholar
  133. Vogel E (1886) Aromatische hautreizende Mittel. In: Vogel, E (ed) Spezielle Arzneimittellehre für Tierärzte. Neff, Stuttgart, 173–192Google Scholar
  134. Wang G-S (1989) Medical uses of Mylabris in ancient china and recent studies. J Ethnopharmacol 26:147–162PubMedGoogle Scholar
  135. Wei C-M, Hansen BS, Vaughan MH, McLaughlin CS (1974) Mechanism of Action of the Mycotoxin Trichodermin, a 12,13-Epoxytrichothecene. Proc Nat Acad Sci USA 71:713–717PubMedGoogle Scholar
  136. Wu X, Flatt PM, Xu H, Mahmud T (2009) Biosynthetic gene cluster of Centoniacytone A, an unusual aminocyclitol from the endosymbiotic bacterium Actinomyces sp. Lu 9419. Chem Biochem 10:304–314Google Scholar
  137. Wu X, Duan H, Tian T, Yao N, Zhou H, Zhang L (2010) Effect of the hfq gene on 2,4-diacetylphloroglucinol production and the Pcol/PcoR quorum-sensing system in Pseudomonas fluorescens 2P24. FEMS Microbiol Lett 309:16–24Google Scholar
  138. Xu Y, Orozco R, Wijeratne KEM, Espinosa-Artiles P, Gunatilaka LAA, Stock PS, Molnár I (2009) Biosynthesis of the cyclooligomer depsipeptide bassianolide, an insecticidal virulence factor of Beauveria bassiana. Fungal Genet Biol 14:353–364Google Scholar
  139. Yoshida N, Oeda K, Watanabe E, Mikami T, Fukita Y, Nishimura K, Komai K, Matsuda K (2001) Chaperonin turned insect toxin. Nature 411:44PubMedGoogle Scholar
  140. Yu X-P, Zhu J-L, Yao X-P, He S-C, Huang H-N, Chen W-L, Hu Y-H, Li D-B (2005) Identification of anrF gene, a homology of admM of andrimid biosynthetic gene cluster related to the antagonistic activity of Enterobacter cloacae B8. World J Gastrenterol 11:6152–6158Google Scholar
  141. Zheng LH, Bao YL, Wu Y, Yu CL, Meng XY, Li YX (2008) Cantharidin reverses multidrug resistance of human hepatoma HepG2/ADM cells via down-regulation of P-glycoprotein expression. Cancer Lett 272:102–109PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Department of Animal Ecology IIUniversity BayreuthBayreuthGermany

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