Chemistry of the Amanita Peptide Toxins

  • Jonathan Walton


Extraordinary advances in scientific methodologies during the nineteenth and twentieth centuries enabled chemists to isolate and characterize biologically active molecules from all branches of the tree of life. Biochemicals (such as DNA, RNA, proteins, and lipids) that are essential for the basic cellular processes of life are known as primary metabolites, whereas other chemicals found in living organisms that have subsidiary roles, often in mediating interactions between organisms, are known as secondary metabolites, specialized metabolites, or natural products (Demain and Fang 2000). There are tens of thousands of known natural products, which are especially prevalent in some taxa of bacteria, fungi, and plants. Ecologically, natural products commonly behave as attractants, repellents, and behavioral modulators. Many have been adopted for human use, for example, caffeine and penicillin. The possible ecological functions of the Amanita cyclic peptide toxins are discussed in Chap.  6.


  1. Abel JJ, Ford WW (1907) On the poisons of Amanita phalloides. J Biol Chem 2:273–288Google Scholar
  2. Abraham WR (2001) Bioactive sesquiterpenes produced by fungi: are they useful for humans as well? Curr Med Chem 8:583–606CrossRefGoogle Scholar
  3. Abuknesha RA, Maragkou A (2004) A highly sensitive and specific enzyme immunoassay for detection of beta-amanitin in biological fluids. Anal Bioanal Chem 379:853–860. CrossRefPubMedGoogle Scholar
  4. Agger S, Lopez-Gallego F, Schmidt-Dannert C (2009) Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol Microbiol 72:1181–1195. CrossRefPubMedPubMedCentralGoogle Scholar
  5. Alves MJ, Ferreira IC, Dias J, Teixeira V, Martins A, Pintado M (2012) A review on antimicrobial activity of mushroom (Basidiomycetes) extracts and isolated compounds. Planta Med 78:1707–1718. CrossRefPubMedGoogle Scholar
  6. Amodeo P, Saviano G, Borin G, Calderan A, Ruzza P, Tancredi T (1998) Solution conformational analysis of sodium complexed [Gly6]- and [Gly9]-antamanide analogs. J Pept Res 51:180–187CrossRefGoogle Scholar
  7. Anderl J, Faulstich H, Hechler T, Kulke M (2013) Antibody–drug conjugate payloads. Meth Mol Biol 1045:51–70. CrossRefGoogle Scholar
  8. Anderson MO, Shelat AA, Guy RK (2005) A solid-phase approach to the phallotoxins: total synthesis of [Ala7]-phalloidin. J Org Chem 70:4578–4584. CrossRefPubMedGoogle Scholar
  9. Andres RY, Frei W (1987) [125I]amatoxin and anti-amatoxin for radioimmunoassay prepared by a novel approach: chemical and structural considerations. Toxicon 25:915–922CrossRefGoogle Scholar
  10. Andres RY, Frei W, Gautschi K, Vonderschmitt DJ (1986) Radioimmunoassay for amatoxins by use of a rapid, 125I-tracer-based system. Clin Chem 32:1751–1755PubMedGoogle Scholar
  11. Apperley S, Kroeger P, Kirchmair M, Kiaii M, Holmes DT, Garber I (2013) Laboratory confirmation of Amanita smithiana mushroom poisoning. Clin Toxicol 51:249–251. CrossRefGoogle Scholar
  12. Azzolin L, Antolini N, Calderan A, Ruzza P, Sciacovelli M, Marin O, Mammi S, Bernardi P, Rasola A (2011) Antamanide, a derivative of Amanita phalloides, is a novel inhibitor of the mitochondrial permeability transition pore. PLoS One 28:e16280. CrossRefGoogle Scholar
  13. Baumann K, Münter K, Faulstich H (1993) Identification of structural features involved in binding of a-amanitin to a monoclonal antibody. Biochemistry 32:4043–4050CrossRefGoogle Scholar
  14. Baumann K, Zanotti G, Faulstich H (1994) A beta-turn in alpha-amanitin is the most important structural feature for binding to RNA polymerase II and three monoclonal antibodies. Protein Sci 3:750–756. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Benjamin DR (1995) Mushrooms: poisons and panaceas. A handbook for naturalists, mycologists, and physicians. WH Freeman, New YorkGoogle Scholar
  16. Bernheimer AW, Oppenheim JD (1987) Some properties of flammutoxin from the edible mushroom Flammulina velutipes. Toxicon 25:1145–1152CrossRefGoogle Scholar
  17. Beuhler M, Lee DC, Gerkin R (2004) The Meixner test in the detection of alpha-amanitin and false-positive reactions caused by psilocin and 5-substituted tryptamines. Ann Emerg Med 44:114–120. CrossRefPubMedGoogle Scholar
  18. Beutler JA, Der Marderosian AH (1981) Chemical variation in Amanita. J Nat Prod 44:422–444CrossRefGoogle Scholar
  19. Beutler JA, Vergeer PP (1980) Amatoxins in American mushrooms: evaluation of the Meixner test. Mycologia 72:1142–1149CrossRefGoogle Scholar
  20. Bhaskaran R, Yu C (1994) NMR spectra and restrained molecular dynamics of the mushroom toxin viroisin. Int J Pept Protein Res 43:393–401CrossRefGoogle Scholar
  21. Bresinsky A, Besl H (1990) A colour atlas of poisonous fungi. Wolfe Publishing, RegensburgGoogle Scholar
  22. Brueckner F, Cramer P (2008) Structural basis of transcription inhibition by alpha-amanitin and implications for RNA polymerase II translocation. Nat Struct Mol Biol 15:811–818. CrossRefGoogle Scholar
  23. Brüggemann O, Meder M, Freitag R (1996) Analysis of amatoxins alpha-amanitin and beta-amanitin in toadstool extracts and body fluids by capillary zone electrophoresis with photodiode array detection. J Chromatogr A 744:167–176CrossRefGoogle Scholar
  24. Buku A, Faulstich H, Wieland T, Dabrowski J (1980a) 2,3-trans-3,4-trans-3,4-Dihydroxy-L-proline: an amino acid in toxic peptides of Amanita virosa mushrooms. Proc Natl Acad Sci U S A 77:2370–2371CrossRefGoogle Scholar
  25. Buku A, Wieland T, Bodenmüller H, Faulstich H (1980b) Amaninamide, a new toxin of Amanita virosa mushrooms. Experientia 36:33–34CrossRefGoogle Scholar
  26. Bushnell DA, Cramer P, Kornberg RD (2002) Structural basis of transcription: alpha-amanitin-RNA polymerase II cocrystal at 2.8 Å resolution. Proc Natl Acad Sci U S A 99:1218–1222. CrossRefPubMedPubMedCentralGoogle Scholar
  27. Chen N, Bowles MR, Pond SM (1993) Polyclonal amanitin-specific antibodies: production and cytoprotective properties in vitro. Biochem Pharmacol 46:327–329CrossRefGoogle Scholar
  28. Chiang CC, Karle IL, Wieland T (1982) Unusual intramolecular hydrogen bonding in cycloamanide A, cyclic (LPro-LVal-LPhe-LPhe-LAla-Gly). A crystal structure analysis. Int J Pept Protein Res 20:414–420CrossRefGoogle Scholar
  29. Chilton W (1994) The chemistry and mode of action of mushroom toxins. In: Spoerke DG, Rumack BH (eds) Handbook of mushroom poisoning: diagnosis and treatment. CRC Press, Boca Raton, pp 165–231Google Scholar
  30. Chilton W, Decato L, Malone M (1973) The unsaturated norleucines of Amanita solitaria, chemical and pharmacologic studies. Lloydia 36:169–173PubMedGoogle Scholar
  31. Clarke DB, Lloyd AS, Robb P (2012) Application of liquid chromatography coupled to time-of-flight mass spectrometry separation for rapid assessment of toxins in Amanita mushrooms. Anal Meth 4:1298–1309CrossRefGoogle Scholar
  32. Courtillot M, Staron T (1970) Amanita virosa Fr. Précision sur l’espèce mise en evidence de sa toxine principale (virosine). Ann Phytopathol 2:561–584Google Scholar
  33. Dal Pozzo A, Esposito E, Ni M, Muzi L, Pisano C, Bucci F, Vesci L, Castorina M, Penco S (2010) Conjugates of a novel 7-substituted camptothecin with RGD-peptides as αvβ3 integrin ligands: an approach to tumor-targeted therapy. Bioconjug Chem 21:1956–1967. CrossRefPubMedGoogle Scholar
  34. De Lamo Marin S, Catala C, Kumar SR, Valleix A, Wagner A, Mioskowski C (2010) A practical and efficient total synthesis of potent insulinotropic (2S,3R,4S)-4-hydroxyisoleucine through a chiral N-protected γ-keto-α-aminoester. Eur J Org Chem 2010:3985–3989CrossRefGoogle Scholar
  35. Demain AL, Fang A (2000) The natural functions of secondary metabolites. Adv Biochem Eng Biotechnol 69:1–39PubMedGoogle Scholar
  36. Deng WQ, Li TH, Xi PG, Gan LX, Xiao ZD, Jiang ZD (2011) Peptide toxin components of Amanita exitialis basidiocarps. Mycologia 103:946–949. CrossRefPubMedGoogle Scholar
  37. Duffy TJ (2008) Toxic fungi of western North America. Available online at Retrieved Dec 2016
  38. Edagwa BJ, Taylor CM (2009) Peptides containing γ,δ-dihydroxy-L-leucine. J Org Chem 74:4132–4136. CrossRefPubMedGoogle Scholar
  39. Enjalbert F, Gallion C, Jehl F, Monteil H, Faulstich H (1992) Simultaneous assay for amatoxins and phallotoxins in Amanita phalloides Fr. by high-performance liquid chromatography. J Chromatogr 598:227–236CrossRefGoogle Scholar
  40. Enjalbert F, Cassanas G, Rapior S, Renault C, Chaumont JP (2004) Amatoxins in wood-rotting Galerina marginata. Mycologia 96:720–729CrossRefGoogle Scholar
  41. Fahrenholz F, Faulstich H, Wieland T (1971) Über die Giftstoffe des grünen Knollenblätterpilzes, XLII: Über Peptidsynthesen, XLVIII. Synthese des Norphalloins und eines Monocyclus mit 18 gliedrigem Ring. Liebigs Ann Chem 743:83–94CrossRefGoogle Scholar
  42. Falcigno L, Costantini S, D’Auria G, Bruno BM, Zobeley S, Zanotti G, Paolillo L (2001) Phalloidin synthetic analogues: structural requirements in the interaction with F-actin. Chemistry 7:4665–4673CrossRefGoogle Scholar
  43. Faulstich H, Georgopoulos D, Bloching M, Wieland T (1974) Analysis of the toxins of amanitin-containing mushrooms. Z Naturforsch 29c:86–88Google Scholar
  44. Faulstich H, Trischmann H, Zobeley S (1975) A radioimmunoassay for amanitin. FEBS Lett 56:312–315CrossRefGoogle Scholar
  45. Faulstich H, Buku A, Bodenmüller H, Wieland T (1980) Virotoxins: actin-binding cyclic peptides of Amanita virosa mushrooms. Biochemistry 19:3334–3343. CrossRefPubMedGoogle Scholar
  46. Faulstich H, Zobeley S, Trischmann H (1982) A rapid radioimmunoassay, using a nylon support, for amatoxins from Amanita mushrooms. Toxicon 20:913–924CrossRefGoogle Scholar
  47. Faulstich H, Bühring HJ, Seitz J (1983) Physical properties and function of phallolysin. Biochemistry 22:4574–4580CrossRefGoogle Scholar
  48. Feng L, Tan L, Li H, Xu Z, Shen G, Tang Y (2015) Selective fluorescent sensing of α-amanitin in serum using carbon quantum dots-embedded specificity determinant imprinted polymers. Biosens Bioelectron 69:265–271. CrossRefPubMedGoogle Scholar
  49. Fiume L, Busi C, Campadelli-Fiume G, Franceschi C (1975) Production of antibodies to amanitins as the basis for their radioimmunoassay. Experientia 31:1233–1234CrossRefGoogle Scholar
  50. Ford WW (1906) The toxicological constitution of Amanita phalloides. J Exp Med 8:437–450CrossRefGoogle Scholar
  51. Ford WW (1909) The distribution of poisons in mushrooms. Science 30:97–108. CrossRefPubMedGoogle Scholar
  52. Garcia J, Oliveira A, de Pinho PG, Freitas V, Carvalho A, Baptista P, Pereira E, de Lourdes Bastos M, Carvalho F (2015a) Determination of amatoxins and phallotoxins in Amanita phalloides mushrooms from northeastern Portugal by HPLC-DAD-MS. Mycologia 107:679–687. CrossRefPubMedGoogle Scholar
  53. Garcia J, Costa VM, Baptista P, de Lourdes Bastos M, Carvalho F (2015b) Quantification of alpha-amanitin in biological samples by HPLC using simultaneous UV- diode array and electrochemical detection. J Chromatogr B Anal Technol Biomed Life Sci 997:85–95. CrossRefGoogle Scholar
  54. Gauhe A, Wieland T (1977) Die cycloamanide, monocyclische peptide; isolierung und strukturaufklärung eines cyclischen heptapeptids (CyA B) und zweir cyclischer oktapeptide (CyA C und CyA D). Liebigs Ann Chem 1977:859–868CrossRefGoogle Scholar
  55. Gicquel T, Lepage S, Fradin M, Tribut O, Duretz B, Morel I (2014) Amatoxins (α- and β-amanitin) and phallotoxin (phalloidin) analyses in urines using high-resolution accurate mass LC-MS technology. J Anal Toxicol 38:335–340. CrossRefPubMedGoogle Scholar
  56. Hallen HE, Watling R, Adams GC (2003) Taxonomy and toxicity of Conocybe lactea and related species. Mycol Res 107:969–979CrossRefGoogle Scholar
  57. Hara R, Kino K (2009) Characterization of novel 2-oxoglutarate dependent dioxygenases converting L-proline to cis-4-hydroxy-L-proline. Biochem Biophys Res Commun 379:882–886. CrossRefGoogle Scholar
  58. He K, Mao Q, Zang X, Zhang Y, Li H, Zhang D (2017) Production of a broad-specificity monoclonal antibody and application as a receptor to detection amatoxins in mushroom. Biologicals 49:57–61. PMID: 28688778. CrossRefPubMedGoogle Scholar
  59. Henderson TJ (2010) Feasibility study for the rapid screening of target molecules using translational diffusion coefficients: diffusion-ordered NMR spectroscopy of biological toxins. Anal Bioanal Chem 396:1465–1471. CrossRefPubMedGoogle Scholar
  60. Herrmann A, Hedman H, Rosén J, Jansson D, Haraldsson B, Hellenäs KE (2012) Analysis of the mushroom nephrotoxin orellanine and its glucosides. J Nat Prod 75:1690–1696. CrossRefPubMedGoogle Scholar
  61. Hutchinson LJ, Madzia SE, Barron GL (1996) The presence and antifeedant function of toxin-producing secretory cells on hyphae of the lawn-inhabiting agaric Conocybe lactea. Can J Bot 74:431–434CrossRefGoogle Scholar
  62. Isernia C, Falcigno L, Macura S, Paolillo L, Pastore AL, Zanotti G (1996) Elucidation of the structure of constrained bicyclopeptides in solution by two-dimensional cross-relaxation spectroscopy: amatoxin analogues. J Pept Sci 2:3–13. CrossRefPubMedGoogle Scholar
  63. Jansson D, Fredriksson SÅ, Herrmann A, Nilsson C (2012) A concept study on identification and attribution profiling of chemical threat agents using liquid chromatography-mass spectrometry applied to Amanita toxins in food. Forensic Sci Int 221:44–49. CrossRefPubMedGoogle Scholar
  64. Jin Z (2013) Muscarine, imidazole, oxazole and thiazole alkaloids. Nat Prod Rep 30:869–915. CrossRefPubMedGoogle Scholar
  65. Kahl JU, Vlasov GP, Seeliger A, Wieland T (1984) Analogs of viroidin. Synthesis of four virotoxin-like F-actin binding heptapeptides with one less hydroxyl group in the dihydroxy-proline ring. Int J Pept Protein Res 23:543–550CrossRefGoogle Scholar
  66. Kaplan CD, Larsson KM, Kornberg RD (2008) The RNA polymerase II trigger loop functions in substrate selection and is directly targeted by alpha-amanitin. Mol Cell 30:547–556. CrossRefPubMedPubMedCentralGoogle Scholar
  67. Kirchmair M, Carrilho P, Pfab R, Haberl B, Felgueiras J, Carvalho F, Cardoso J, Melo I, Vinhas J, Neuhauser S (2012) Amanita poisonings resulting in acute, reversible renal failure: new cases, new toxic Amanita mushrooms. Nephrol Dial Transplant 27:1380–1386. CrossRefPubMedGoogle Scholar
  68. Kosentka P, Sprague SL, Ryberg M, Gartz J, May AL, Campagna SR, Matheny PB (2013) Evolution of the toxins muscarine and psilocybin in a family of mushroom-forming fungi. PLoS One 8:e64646. CrossRefPubMedPubMedCentralGoogle Scholar
  69. Kostansek EC, Lipscomb WN, Yocum RR, Thiessen WE (1978) Conformation of the mushroom toxin β-amanitin in the crystalline state. Biochemistry 17:3790–3795CrossRefGoogle Scholar
  70. Krogsgaard-Larsen P, Hansen JJ (1992) Naturally-occurring excitatory amino acids as neurotoxins and leads in drug design. Toxicol Lett 64-65:409–416CrossRefGoogle Scholar
  71. Laatsch H, Matthies L (1992) Letter to the editor. Experientia 48:533–534Google Scholar
  72. Lee S, Nam S-J, Hyun C (2009) Mushroom poisoning by Inocybe fastigiata in a maltese dog. J Anim Vet Adv 8:708–710Google Scholar
  73. Leite M, Freitas A, Azul AM, Barbosa J, Costa S, Ramos F (2013) Development, optimization and application of an analytical methodology by ultra performance liquid chromatography-tandem mass spectrometry for determination of amanitins in urine and liver samples. Anal Chim Acta 799:77–87. CrossRefPubMedGoogle Scholar
  74. Letschert K, Faulstich H, Keller D, Keppler D (2006) Molecular characterization and inhibition of amanitin uptake into human hepatocytes. Toxicol Sci 91:140–149. CrossRefPubMedGoogle Scholar
  75. Li P, Deng WQ, Li TH, Song B, Shen YH (2013) Illumina-based de novo transcriptome sequencing and analysis of Amanita exitialis basidiocarps. Gene 532:63–71. CrossRefPubMedGoogle Scholar
  76. Li P, Deng W, Li T (2014) The molecular diversity of toxin gene families in lethal Amanita mushrooms. Toxicon 83:59–68. CrossRefGoogle Scholar
  77. Litten W (1975) The most poisonous mushrooms. Sci Am 232:90–101. CrossRefPubMedGoogle Scholar
  78. Little MC, Preston JF 3rd, Jackson C, Bonetti S, King RW, Taylor LC (1986) Alloviroidin, the naturally occurring toxic isomer of the cyclopeptide viroidin. Biochemistry 25:2867–2872CrossRefGoogle Scholar
  79. Liu Y, Zhang X, Han C, Wan G, Huang X, Ivan C, Jiang D, Rodriguez-Aguayo C, Lopez-Berestein G, Rao PH, Maru DM, Pahl A, He X, Sood AK, Ellis LM, Anderl J, Lu X (2015) TP53 loss creates therapeutic vulnerability in colorectal cancer. Nature 520:697–701. CrossRefPubMedPubMedCentralGoogle Scholar
  80. Loranger A, Tuchweber B, Gicquaud C, St-Pierre S, Côté MG (1985) Toxicity of peptides of Amanita virosa mushrooms in mice. Fundam Appl Toxicol 5:1144–1152. CrossRefPubMedGoogle Scholar
  81. Luo H, Hallen-Adams HE, Scott-Craig JS, Walton JD (2012) Ribosomal biosynthesis of α-amanitin in Galerina marginata. Fungal Genet Biol 49:123–129. CrossRefPubMedGoogle Scholar
  82. Luo H, Hong SY, Sgambelluri RM, Angelos E, Li X, Walton JD (2014) Peptide macrocyclization catalyzed by a prolyl oligopeptidase involved in α-amanitin biosynthesis. Chem Biol 21:1610–1617. CrossRefPubMedPubMedCentralGoogle Scholar
  83. Luo H, DuBois B, Sgambelluri RM, Angelos ER, Li X, Holmes D, Walton JD (2015) Production of 15N-labeled α-amanitin in Galerina marginata. Toxicon 103:60–64. CrossRefGoogle Scholar
  84. Lutter LC, Faulstich H (1984) Affinity isolation of RNA polymerase II on amanitin-sepharose. Biochem Biophys Res Commun 119:42–48CrossRefGoogle Scholar
  85. Lutz C, Müller C, Simon W (2014) Methods for synthesizing amatoxin building block and amatoxins. Eur Patent App EP 2 684 865 A1Google Scholar
  86. Lynen F, Wieland H (1938) Über die Giftstoffe des grünen Knollenblätterpilzes, IV: Kristallisation von Phalloidin. Liebigs Ann Chem 533:93–117CrossRefGoogle Scholar
  87. Matinkhoo K, Pryyma A, Todorovic M, Patrick BO, Perrin DM (2018) Synthesis of the death-cap mushroom toxin α-amanitin. J Amer Chem Soc, in press.
  88. Matsuura M, Saikawa Y, Inui K, Nakae K, Igarashi M, Hashimoto K, Nakata M (2009) Identification of the toxic trigger in mushroom poisoning. Nat Chem Biol 5:465–467. CrossRefPubMedGoogle Scholar
  89. Matthies L, Laatsch H (1991) Cortinarins in Cortinarius speciosissimus? A critical revision. Experientia 47:634–640CrossRefGoogle Scholar
  90. May JP, Perrin DM (2007) Tryptathionine bridges in peptide synthesis. Biopolymers 88:714–724. CrossRefPubMedGoogle Scholar
  91. May JP, Perrin DM (2008) Intraannular Savige–Fontana reaction: one-step conversion of one class of monocyclic peptides into another class of bicyclic peptides. Chemistry 14:3404–3409. CrossRefPubMedGoogle Scholar
  92. May JP, Fournier P, Pellicelli J, Patrick BO, Perrin DM (2005) High yielding synthesis of 3a-hydroxypyrrolo[2,3-b]indoline dipeptide methyl esters: synthons for expedient introduction of the hydroxypyrroloindoline moiety into larger peptide-based natural products and for the creation of tryptathionine bridges. J Org Chem 70:8424–8430. CrossRefPubMedGoogle Scholar
  93. May JP, Fournier P, Patrick BO, Perrin DM (2008) Synthesis, characterisation, and in vitro evaluation of Pro2-Ile3-S-deoxo-amaninamide and Pro2-D-allo-Ile3-S-deoxo-amaninamide: implications for structure-activity relationships in amanitin conformation and toxicity. Chemistry 14:3410–3417. CrossRefPubMedGoogle Scholar
  94. Meixner A (1979) Amatoxin-nachweis in pilzen. Z Mykol 45:137–139Google Scholar
  95. Michelot D, Melendez-Howell LM (2003) Amanita muscaria: chemistry, biology, toxicology, and ethnomycology. Mycol Res 107:131–146CrossRefGoogle Scholar
  96. Morris PW, Venton DL, Kelley KM (1978) Biochemistry of the amatoxins: preparation and characterization of a stable iodinated α-amanitin. Biochemistry 17:690–698CrossRefGoogle Scholar
  97. Munekata E (1981) New advances in phallotoxin chemistry. In: Eberle A, Geiger R, Wieland T (eds) Perspectives in peptide chemistry. Karger, Basel, pp 129–140Google Scholar
  98. Munekata E, Faulstich H, Wieland T (1977) Über die Inhaltsstoffe des grünen knollenblätterpilzes. LIII. Totalsynthese von Phalloin und Leu7-phalloin. Liebigs Ann Chem 1977:1758–1765CrossRefGoogle Scholar
  99. Muraoka S, Fukamachi N, Mizumoto K, Shinozawa T (1999) Detection and identification of amanitins in the wood-rotting fungi Galerina fasciculata and Galerina helvoliceps. Appl Environ Microbiol 65:4207–4210PubMedPubMedCentralGoogle Scholar
  100. Nakamori T, Suzuki A (2007) Defensive role of cystidia against Collembola in the basidiomycetes Russula bella and Strobilurus ohshimae. Mycol Res 111:1345–1351. CrossRefPubMedGoogle Scholar
  101. Olson KR, Pond SM, Seward J, Healey K, Woo OF, Becker CE (1982) Amanita phalloides-type mushroom poisoning. West J Med 137:282–289Google Scholar
  102. Patel DJ, Tonelli AE, Pfaender P, Faulstich H, Wieland T (1973) Experimental and calculated conformational characteristics of the bicyclic heptapeptide phalloidin. J Mol Biol 79:185–196CrossRefGoogle Scholar
  103. Pehk T, Haga M, Vija H, Lippman E (1989) High-field 2D NMR spectroscopy of amanitin isomers. Mag Res Chem 27:173–183. CrossRefGoogle Scholar
  104. Pelizzari V, Feifel E, Rohrmoser MM, Gstraunthaler G, Moser M (1994) Partial purification and characterization of a toxic component of Amanita smithiana. Mycologia 86:555–560CrossRefGoogle Scholar
  105. Pulman JA, Childs KL, Sgambelluri RM, Walton JD (2016) Expansion and diversification of the MSDIN family of cyclic peptide genes in the poisonous agarics Amanita phalloides and A. bisporigera. BMC Genomics 17:1038. CrossRefPubMedPubMedCentralGoogle Scholar
  106. Riley R, Salamov AA, Brown DW, Nagy LG, Floudas D, Held BW, Levasseur A, Lombard V, Morin E, Otillar R, Lindquist EA, Sun H, LaButti KM, Schmutz J, Jabbour D, Luo H, Baker SE, Pisabarro AG, Walton JD, Blanchette RA, Henrissat B, Martin F, Cullen D, Hibbett DS, Grigoriev IV (2014) Extensive sampling of basidiomycete genomes demonstrates inadequacy of the white-rot/brown-rot paradigm for wood decay fungi. Proc Natl Acad Sci U S A 111:9923–9928. CrossRefPubMedPubMedCentralGoogle Scholar
  107. Ritorto MS, Cook K, Tyagi K, Pedrioli PGA, Trost M (2013) Hydrophilic strong anion exchange (hSAX) chromatography for highly orthogonal peptide separation of complex proteomes. J Proteome Res 12:2449–2457. CrossRefPubMedPubMedCentralGoogle Scholar
  108. Ruzza P, Calderan A, Biondi B, Carrara M, Tancredi T, Borin G (1999) Ion binding and pharmacological properties of Tyr6 and Tyr9 antamanide analogs. J Pept Res 53:442–452CrossRefGoogle Scholar
  109. Savige WE, Fontana A (1980) A novel synthesis of 2-thioether derivatives of tryptophan. Covalent binding of tryptophan to cysteine sulfhydryl groups in peptides and proteins. Int J Pept Protein Res 15:102–112CrossRefGoogle Scholar
  110. Saviuc P, Danel V (2006) New syndromes in mushroom poisoning. Toxicol Rev 25:199–209CrossRefGoogle Scholar
  111. Schneider P, Bouhired S, Hoffmeister D (2008) Characterization of the atromentin biosynthesis genes and enzymes in the homobasidiomycete Tapinella panuoides. Fungal Genet Biol 45:1487–1496. CrossRefPubMedGoogle Scholar
  112. Schuresko LA, Lokey RS (2007) A practical solid-phase synthesis of Glu7-phalloidin and entry into fluorescent F-actin binding reagents. Angew Chem Int Ed 46:3547–3549. CrossRefGoogle Scholar
  113. Seeger R (1984) Zeitungspapiertest für Amanitine—falsch-positive Ergebnisse. Z Mykol 50:353–359Google Scholar
  114. Sgambelluri RM, Epis S, Sassera D, Luo H, Angelos ER, Walton JD (2014) Profiling of amatoxins and phallotoxins in the genus Lepiota by liquid chromatography combined with UV absorbance and mass spectrometry. Toxins 6:2336–2347. CrossRefPubMedPubMedCentralGoogle Scholar
  115. Sgambelluri RM, Smith MO, Walton JD (2018) Versatility of prolyl oligopeptidase B in peptide macrocyclization. ACS Synth Biol 7:145–152. CrossRefPubMedGoogle Scholar
  116. Shi X, Miyakawa T, Nakamura A, Hou F, Hibi M, Ogawa J, Kwon Y, Tanokura M (2017) Engineering a short-chain dehydrogenase/reductase for the stereoselective production of (2S,3R,4S)-4-hydroxyisoleucine with three asymmetric centers. Sci Rep 7:13703. CrossRefPubMedPubMedCentralGoogle Scholar
  117. Shoham G, Lipscomb WN, Wieland T (1989) Conformations of amatoxins in the crystalline state. J Am Chem Soc 111:4791–4809. Scholar
  118. Skillman KM, Diraviyam K, Khan A, Tang K, Sept D, Sibley LD (2011) Evolutionarily divergent, unstable filamentous actin is essential for gliding motility in apicomplexan parasites. PLoS Pathog 7:e1002280. CrossRefPubMedPubMedCentralGoogle Scholar
  119. Sliva D (2004) Cellular and physiological effects of Ganoderma lucidum (Reishi). Mini Rev Med Chem 4:873–879CrossRefGoogle Scholar
  120. Spoerke DG, Rumack BH (1994) Handbook of mushroom poisoning. CRC Press, Boca RatonGoogle Scholar
  121. Stasyk T, Lutsik-Kordovsky M, Wernstedt C, Antonyuk V, Klyuchivska O, Souchelnytskyi S, Hellman U, Stoika R (2010) A new highly toxic protein isolated from the death cap Amanita phalloides is an L-amino acid oxidase. FEBS J 277:1260–1269. CrossRefPubMedGoogle Scholar
  122. Stebelska K (2013) Fungal hallucinogens psilocin, ibotenic acid, and muscimol: analytical methods and biologic activities. Ther Drug Monit 35:420–442. CrossRefPubMedGoogle Scholar
  123. Stijve T, Seeger R (1979) Determination of α-, β-, and γ-amanitin by high performance thin-layer chromatography in Amanita phalloides (Vaill. ex Fr.) Secr. from various origin. Z Naturforsch 34C:1133–1138Google Scholar
  124. Tebbett IR (1992) Letter to the editor. Experientia 48:532–533CrossRefGoogle Scholar
  125. Tebbett IR, Caddy B (1984) Mushroom toxins of the genus Cortinarius. Experientia 40:441–446CrossRefGoogle Scholar
  126. Thomas JP, Arzoomanian R, Alberti D, Feierabend C, Binger K, Tutsch KD, Steele T, Marnocha R, Smith C, Smith S, MacDonald J, Wilding G, Bailey H (2001) Phase I clinical and pharmacokinetic trial of irofulven. Cancer Chemother Pharmacol 48:467–472CrossRefGoogle Scholar
  127. Tomková J, Ondra P, Válka I (2015) Simultaneous determination of mushroom toxins α-amanitin, β-amanitin and muscarine in human urine by solid-phase extraction and ultra-high-performance liquid chromatography coupled with ultra-high-resolution TOF mass spectrometry. Forensic Sci Int 251:209–213. CrossRefPubMedGoogle Scholar
  128. Tuno N, Takahashi KH, Yamashita H, Osawa N, Tanaka C (2007) Tolerance of Drosophila flies to ibotenic acid poisons in mushrooms. J Chem Ecol 33:311–317. CrossRefPubMedGoogle Scholar
  129. Vergeer PP (1983) The Meixner test. West J Med 138:576PubMedPubMedCentralGoogle Scholar
  130. Wang Q, Ouazzani J, Sasaki NA, Potier P (2002) A practical synthesis of (2S,3R,4S)-4-hydroxyleucine, a potent insulinotropic α-amino acid from fenugreek. Eur J Org Chem 2002:834–839CrossRefGoogle Scholar
  131. Wei J, Wu J, Chen J, Wu B, He Z, Zhang P, Li H, Sun C, Liu C, Chen Z, Xie J (2017) Determination of cyclopeptide toxins in Amanita subpallidorosea and Amanita virosa by high-performance liquid chromatography coupled with high-resolution mass spectrometry. Toxicon 133:26–32. CrossRefPubMedGoogle Scholar
  132. West PL, Lindgren J, Horowitz BZ (2009) Amanita smithiana mushroom ingestion: a case of delayed renal failure and literature review. J Med Toxicol 5:32–38CrossRefGoogle Scholar
  133. Wieczorek Z, Siemion IZ, Zimecki M, Bolewska-Pedyczak E, Wieland T (1993) Immunosuppressive activity in the series of cycloamanide peptides from mushrooms. Peptides 14:1–5CrossRefGoogle Scholar
  134. Wieland T (1983) The toxic peptides from Amanita mushrooms. Int J Pept Protein Res 22:257–276CrossRefGoogle Scholar
  135. Wieland T (1986) Peptides of poisonous Amanita mushrooms. Springer, BerlinCrossRefGoogle Scholar
  136. Wieland T, Boehringer W (1960) Über die Giftstoffe des grünen Knollenblätterpilzes, XIX: Umwandlung von β-amanitin in α-amanitin. Liebigs Ann Chem 635:178–181CrossRefGoogle Scholar
  137. Wieland T, Faulstich H (1991) Fifty years of amanitin. Experientia 47:1186–1193CrossRefGoogle Scholar
  138. Wieland T, Götzendörfer C, Zanotti G, Vaisius AC (1981) The effect of the chemical nature of the side chains of amatoxins in the inhibition of eukaryotic RNA polymerase B. Eur J Biochem 117:161–164CrossRefGoogle Scholar
  139. Wieland H, Hallermayer R (1941) Über die Giftstoffe des grünen Knollenblätterpilzes, VI: Amanitin, das Hauptgift des Knollenblätterpilzes. Liebigs Ann Chem 548:1–18CrossRefGoogle Scholar
  140. Wieland T, Schnabel HW (1962a) Über die Giftstoffe des grünen Knollenblätterpilzes, XXI: Die Konstitution des Phallacidins. Liebigs Ann Chem 657:218–225CrossRefGoogle Scholar
  141. Wieland T, Schnabel HW (1962b) Über die Giftstoffe des grünen Knollenblätterpilzes, XXII: Neue Sequenzanalyse von Phalloidin und Phalloin. Liebigs Ann Chem 657:225–228CrossRefGoogle Scholar
  142. Wieland T, Wirth L, Fischer E (1949) Über die Giftstoffe des Knollenblätterpilzes VII: β-Amanitin, eine dritte Komponente des Knollenblätterpilzgiftes. Liebigs Ann Chem 564:152–160CrossRefGoogle Scholar
  143. Wieland T, Miura T, Seeliger A (1983) Analogs of phalloidin. D-Abu2-Lys7-phalloin, an F-actin binding analog, its rhodamine conjugate (RLP) a novel fluorescent F-actin-probe, and D-Ala2-Leu7-phalloin, an inert peptide. Int J Pept Protein Res 21:3–10CrossRefGoogle Scholar
  144. Wulf E, Deboben A, Bautz FA, Faulstich H, Wieland T (1979) Fluorescent phallotoxin, a tool for the visualization of cellular actin. Proc Natl Acad Sci U S A 76:4498–4502CrossRefGoogle Scholar
  145. Xue JH, Wu P, Chi YL, Xu LX, Wei XY (2011) Cyclopeptides from Amanita exitialis. Nat Prod Bioprospect 1:52–66CrossRefGoogle Scholar
  146. Yamaura Y, Fukuhara M, Takabatake E, Ito N, Hashimoto T (1986) Hepatotoxic action of a poisonous mushroom, Amanita abrupta in mice and its toxic component. Toxicology 38:161–173CrossRefGoogle Scholar
  147. Yang WS, Lin CH, Huang JW, Fang CC (2006) Acute renal failure caused by mushroom poisoning. J Formos Med Assoc 105:263–267. CrossRefPubMedGoogle Scholar
  148. Zanotti G, Birr C, Wieland T (1981) Analogs of amanin: synthesis of Ile3-amaninamide and its diastereoisomeric (S)-sulfoxide. Int J Pept Protein Res 18:162–168CrossRefGoogle Scholar
  149. Zanotti G, Möhringer C, Wieland T (1987) Synthesis of analogues of amaninamide, an amatoxin from the white Amanita virosa mushroom. Int J Pept Protein Res 30:450–459CrossRefGoogle Scholar
  150. Zanotti G, Petersen G, Wieland T (1992) Structure-toxicity relationships in the amatoxin series. Structural variations of side chain 3 and inhibition of RNA polymerase II. Int J Pept Protein Res 40:551–558CrossRefGoogle Scholar
  151. Zanotti G, Kobayashi N, Munekata E, Zobeley S, Faulstich H (1999) D-configuration of serine is crucial in maintaining the phalloidin-like conformation of viroisin. Biochemistry 38:10723–10729. CrossRefPubMedGoogle Scholar
  152. Zanotti G, Falcigno L, Saviano M, D'Auria G, Bruno BM, Campanile T, Paolillo L (2001) Solid state and solution conformation of [Ala7]-phalloidin: a synthetic phallotoxin analogue. Chemistry 7:1479–1485CrossRefGoogle Scholar
  153. Zhao L, May JP, Blanc A, Dietrich DJ, Loonchanta A, Matinkhoo K, Pryyma A, Perrin DM (2015) Synthesis of a cytotoxic amanitin for bio-orthogonal conjugation. Chembiochem 16:1420–1425. CrossRefGoogle Scholar
  154. Zhou ZY, Shi GQ, Fontaine R, Wei K, Feng T, Wang F, Wang GQ, Qu Y, Li ZH, Dong ZJ, Zhu HJ, Yang ZL, Zeng G, Liu JK (2012) Evidence for the natural toxins from the mushroom Trogia venenata as a cause of sudden unexpected death in Yunnan Province, China. Angew Chem Int Ed Eng 51:2368–2370. CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Jonathan Walton
    • 1
  1. 1.United States Department of Energy Plant Research Lab and Department of Plant BiologyMichigan State UniversityEast LansingUSA

Personalised recommendations