Distribution and Taxonomic Variation in the Amanita Cyclic Peptide Toxins

  • Jonathan Walton


The literature on the taxonomic and tissue distribution of the Amanita cyclic peptides is extensive. Dating from the earliest day of toxin research, many studies have surveyed different mushroom species, specimens of the same species, growing environments, mushroom development stages, and mushroom tissues. It would be an encyclopedic and not very informative exercise to tabulate all of the results, not just because of their number but because many of the different studies are not easily comparable due to the use of different methods of toxin extraction and quantitation (or lack thereof) and the frequent omission of sufficient descriptions of the samples to allow species identifications. For an earlier summary of knowledge about the distribution of toxins among species and tissues, see Wieland (1986).


  1. Ammirati JF, Thiers HD, Horgen PA (1977) Amatoxin-containing mushrooms: Amanita ocreata and A. phalloides in California. Mycologia 69:1095–1108CrossRefGoogle Scholar
  2. Ben Khelil M, Zhioua M, Bakir O, Allouche M, Gloulou F, Banasr A, Haouet S, Hedhili A, Hamdoun M (2010) Intoxication mortelle par Lepiota brunnioincarnata: à propos de 4 cas. Ann Biol Clin (Paris) 68:561–567. CrossRefGoogle Scholar
  3. Benedict RG, Tyler VE Jr, Brady LR, Weber LJ (1966) Fermentative production of amanita toxins by a strain of Galerina marginata. J Bacteriol 91:1380–1381PubMedPubMedCentralGoogle Scholar
  4. Beutler JA, Der Marderosian AH (1981) Chemical variation in Amanita. J Nat Prod (Lloydia) 44:422–431CrossRefGoogle Scholar
  5. Beutler JA, Vergeer PP (1980) Amatoxins in American mushrooms: evaluation of the Meixner test. Mycologia 72:1142–1149CrossRefGoogle Scholar
  6. Brady LR, Benedict RG, Tyler VE, Stuntz DE, Malone MH (1975) Identification of Conocybe filaris as a toxic basidiomycete. Lloydia 38:172–173PubMedGoogle Scholar
  7. Bresinsky A, Besl H (1990) A colour atlas of poisonous fungi. Wolfe Publishing, RegensburgGoogle Scholar
  8. Brown DW, Butchko RA, Busman M, Proctor RH (2012) Identification of gene clusters associated with fusaric acid, fusarin, and perithecial pigment production in Fusarium verticillioides. Fungal Genet Biol 49:521–532. CrossRefPubMedGoogle Scholar
  9. Buku A, Wieland T, Bodenmüller H, Faulstich H (1980) Amaninamide, a new toxin of Amanita virosa mushrooms. Experientia 36:33–34CrossRefGoogle Scholar
  10. Buller AHR (1909) Researches on fungi. Longmans, Green, LondonCrossRefGoogle Scholar
  11. Cai Q, Tulloss RE, Tang LP, Tolgor B, Zhang P, Chen ZH, Yang ZL (2014) Multi-locus phylogeny of lethal amanitas: implications for species diversity and historical biography. BMC Evol Biol 14:143. CrossRefPubMedPubMedCentralGoogle Scholar
  12. Cai Q, Cui YY, Yang ZL (2016) Lethal Amanita in China. Mycologia 108:993–1009. CrossRefGoogle Scholar
  13. Clémençon H (2004) Cytology and plectology of the hymenomycetes. J. Cramer, BerlinGoogle Scholar
  14. 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
  15. Duffy TJ (2008) Toxic fungi of western North America. Available on line at (retrieved December, 2017)
  16. Enjalbert F, Cassanas G, Andary C (1989) Variation in amounts of main phallotoxins in Amanita phalloides. Mycologia 81:266–271CrossRefGoogle Scholar
  17. 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
  18. Enjalbert F, Cassanas G, Guinchard C, Chaumont JP (1996) Toxin composition of Amanita phalloides tissues in relation to the collection site. Mycologia 88:909–921CrossRefGoogle Scholar
  19. Enjalbert F, Cassanas G, Salhi SL, Guinchard C, Chaumont JP (1999) Distribution of the amatoxins and phallotoxins in Amanita phalloides. Influence of the tissues and the collection site. CR Acad Sci III 322:855–862CrossRefGoogle Scholar
  20. Enjalbert F, Rapior S, Nouguier-Soulé J, Guillon S, Amouroux N, Cabot C (2002) Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicol 40:715–757CrossRefGoogle Scholar
  21. Enjalbert F, Cassanas G, Rapior S, Renault C, Chaumont JP (2004) Amatoxins in wood-rotting Galerina marginata. Mycologia 96:720–729. CrossRefPubMedGoogle Scholar
  22. Faulstich H, Cochet-Meilhac M (1976) Amatoxins in edible mushrooms. FEBS Lett 64:73–75CrossRefGoogle Scholar
  23. Faulstich H, Georgopoulos D, Bloching M, Wieland T (1974) Analysis of the toxins of amanitin-containing mushrooms. Z Naturforsch 29c:86–88Google Scholar
  24. Ford WW (1906) The toxicological constitution of Amanita phalloides. J Exp Med 8:437–450CrossRefGoogle Scholar
  25. Ford WW (1909) The distribution of poisons in mushrooms. Science 30:97–108. CrossRefPubMedGoogle Scholar
  26. Furia A, Bernicchia A, Alberton F (1982) Intossicazione parafalloidea da Lepiota brunneo-incarnata. Micol Ital 11:29–34Google Scholar
  27. Garcia J, Oliveira A, de Pinho PG, Freitas V, Carvalho A, Baptista P, Pereira E, de Lourdes BM, Carvalho F (2015) Determination of amatoxins and phallotoxins in Amanita phalloides mushrooms from northeastern Portugal by HPLC-DAD-MS. Mycologia 107:679–687. CrossRefPubMedGoogle Scholar
  28. Gérault A, Girre L (1975) Recherches toxicologiques sur le genre Lepiota Fries. CR Acad Sci, Sér D 280:2841–2843Google Scholar
  29. Gulden G, Dunham S, Stockman J (2001) DNA studies in the Galerina marginata complex. Mycol Res 105:432–440. CrossRefGoogle Scholar
  30. Gulden G, Stensrud O, Shalchian-Tabrizi K, Kauserud H (2005) Galerina Earle: a polyphyletic genus in the consortium of dark-spored agarics. Mycologia 97:823–827. CrossRefPubMedGoogle Scholar
  31. Gull K, Newsam RJ (1975) Ultrastructural organization of cystidia in the basidiomycete Agrocybe praecox. J Gen Microbiol 91:74–78CrossRefGoogle Scholar
  32. Hallen HE, Adams GC, Eicker A (2002) Amatoxins and phallotoxins in indigenous and introduced South African Amanita species. S Afr J Bot 68:322–326CrossRefGoogle Scholar
  33. Hallen HE, Watling R, Adams GC (2003) Taxonomy and toxicity of Conocybe lactea and related species. Mycol Res 107:969–979CrossRefGoogle Scholar
  34. Hallen HE, Luo H, Scott-Craig JS, Walton JD (2007) Gene family encoding the major toxins of lethal Amanita mushrooms. Proc Natl Acad Sci U S A 104:19097–19101. CrossRefPubMedPubMedCentralGoogle Scholar
  35. Horgen PA, Ammirati JF, Thiers HD (1976) Occurence of amatoxins in Amanita ocreata. Lloydia 39:368–371PubMedGoogle Scholar
  36. Hu J, Zhang P, Zeng J, Chen Z (2012) Determination of amatoxins in different tissues and development stages of Amanita exitialis. J Sci Food Agric 92:2664–2667. CrossRefPubMedGoogle Scholar
  37. 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
  38. Jenkins DT (1982) A study of Amanita types. IV Taxa described by G F Atkinson. Mycotaxon 14:237–246Google Scholar
  39. Johnson BC, Preston JF (1979) Unique amatoxin resistance of RNA synthesis in isolated nuclei from Amanita species accumulating amatoxins. Arch Microbiol 122:161–167CrossRefGoogle Scholar
  40. Johnson BEC, Preston JF, Kimbrough JW (1979) Quantitation of amanitins in Galerina autumnalis. Mycologia 68:1248–1252. CrossRefGoogle Scholar
  41. Kaneko H, Tomomasa T, Inoue Y, Kunimoto F, Fukusato T, Muraoka S, Gonmori K, Matsumoto T, Morikawa A (2001) Amatoxin poisoning from ingestion of Japanese Galerina mushrooms. J Toxicol Clin Toxicol 39:413–416CrossRefGoogle Scholar
  42. Kaya E, Yilmaz I, Sinirlioglu ZA, Karahan S, Bayram R, Yaykasli KO, Colakoglu S, Saritas A, Severoglu Z (2013) Amanitin and phallotoxin concentration in Amanita phalloides var. alba mushroom. Toxicon 76:225–233CrossRefGoogle Scholar
  43. Kervégant M, de Haro L, Patat AM, Pons C, Thomachot L, Minodier P (2013) Phalloides syndrome poisoning after ingestion of Lepiota mushrooms. Wilderness Environ Med 24:170–172. CrossRefPubMedGoogle Scholar
  44. Kohler A, Kuo A, Nagy LG, Morin E, Barry KW, Buscot F, Canback B, Choi C, Cichocki N, Clum A, Colpaert J, Copeland A, Costa MD, Dore J, Floudas D, Gay G, Girlanda M, Henrissat B, Herrmann S, Hess J, Hogberg N, Johansson T, Khouja HR, LaButti K, Lahrmann U, Levasseur A, Lindquist EA, Lipzen A, Marmeisse R, Martino E, Murat C, Ngan CY, Nehls U, Plett JM, Pringle A, Ohm RA, Perotto S, Peter M, Riley R, Rineau F, Ruytinx J, Salamov A, Shah F, Sun H, Tarkka M, Tritt A, Veneault-Fourrey C, Zuccaro A, Tunlid A, Grigoriev IV, Hibbett DS, Martin F (2015) Convergent losses of decay mechanisms and rapid turnover of symbiosis genes in mycorrhizal mutualists. Nat Genet 47:410–415. CrossRefPubMedGoogle Scholar
  45. Kose M, Yilmaz I, Akata I, Kaya E, Guler K (2015) A case study: rare Lepiota brunneoincarnata poisoning. Wilderness Environ Med 26:350–354. CrossRefPubMedGoogle Scholar
  46. Kwok OCH, Plattner R, Weisleder D, Wicklow DT (1992) A nematicidal toxin from Pleurotus ostreatus NRRL 3526. J Chem Ecol 18:127–136. CrossRefPubMedGoogle Scholar
  47. 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
  48. Li P, Deng W-Q, Li T-H (2014a) Molecular cloning of α-amanitin and characterization of its expression pattern in different parts and development stages of Amanita exitialis fruitbody. Mycol Progress 13:1011–1016CrossRefGoogle Scholar
  49. Li P, Deng W, Li T (2014b) The molecular diversity of toxin gene families in lethal Amanita mushrooms. Toxicon 83:59–68. CrossRefPubMedGoogle Scholar
  50. Little MC, Preston JF III, Jackson C, Bonetti S, King RW, Taylor LCE (1986) Alloviroidin, the naturally occurring toxic isomer of the cyclopeptide viroidin. Biochemistry 25:2867–2872CrossRefGoogle Scholar
  51. Luo H, Hallen-Adams HE, Walton JD (2009) Processing of the phalloidin proprotein by prolyl oligopeptidase from the mushroom Conocybe albipes. J Biol Chem 284:18070–18077. CrossRefPubMedPubMedCentralGoogle Scholar
  52. Luo H, Hallen-Adams HE, Scott-Craig JS, Walton JD (2010) Co-localization of amanitin and a candidate toxin-processing prolyl oligopeptidase in Amanita basidiocarps. Eukaryot Cell 9:1891–1900. CrossRefPubMedPubMedCentralGoogle Scholar
  53. 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. CrossRefGoogle Scholar
  54. 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. CrossRefGoogle Scholar
  55. Luo H, DuBois B, Sgambelluri RM, Angelos ER, Li X, Holmes D, Walton JD (2015) Production of [15]N-labeled α-amanitin in Galerina marginata. Toxicon 103:60–64. CrossRefPubMedPubMedCentralGoogle Scholar
  56. McKnight TA, McKnight KB, Skeels MC (2010) Amatoxin and phallotoxin concentration in Amanita bisporigera spores. Mycologia 102:763–765. CrossRefGoogle Scholar
  57. Meunier B, Messner M, Bardaxoglou E, Spiliopoulos G, Terblanche J, Launois B (1994) Liver transplantation for severe Lepiota helveola poisoning. Liver 14:158–160. CrossRefGoogle Scholar
  58. Miller OK Jr, Hemmes DE, Wong G (1988) Amanita marmorata subsp. myrtacearum, a new subspecies in Amanita section Phalloideae from Hawaii. Mycologia 88:140–145Google Scholar
  59. Mottram AR, Lazio MP, Bryant SM (2010) Lepiota subincarnata J.E. Lange induced fulminant hepatic failure presenting with pancreatitis. J Med Toxicol 6:155–157. CrossRefPubMedPubMedCentralGoogle Scholar
  60. Mullersman JE, Preston JF (1982) A microassay for phallotoxins: quantification of phallotoxins in Amanita species. Anal Biochem 119:266–273CrossRefGoogle Scholar
  61. Mungenast T (2008) Eulogy for a lost dog. Retrieved 24 Oct 2017
  62. 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
  63. Parnmen S, Sikaphan S, Leudang S, Boonpratuang T, Rangsiruji A, Naksuwankul K (2016) Molecular identification of poisonous mushrooms using nuclear ITS region and peptide toxins: a retrospective study on fatal cases in Thailand. J Toxicol Sci 41:65–76. CrossRefPubMedGoogle Scholar
  64. Paydas S, Kocak R, Erturk F, Erken E, Zaksu HS, Gurcay A (1990) Poisoning due to amatoxin-containing Lepiota species. Br J Clin Pract 44:450–453PubMedGoogle Scholar
  65. Pitkin JW, Nikolskaya A, Ahn JH, Walton JD (2000) Reduced virulence caused by meiotic instability of the TOX2 chromosome of the maize pathogen Cochliobolus carbonum. Mol Plant-Microbe Interact 13:80–87. CrossRefPubMedGoogle Scholar
  66. Preston JF, Stark HJ, Kimbrough JW (1975) Quantitation of amanitins in Amanita verna with calf thymus RNA polymerase B. Lloydia 38:153–161PubMedGoogle Scholar
  67. Preston JF, Johnson BEC, Little M, Romeo T, Stark HJ, Mullersman JE (1982) Investigations on the function of amatoxins in Amanita species: a case for amatoxins as potential regulators of transcription. In: Kleinkauf H, von Döhren H (eds) Peptide antibiotics: biosynthesis and functions. Walter de Gruyter, Berlin, pp 399–426Google Scholar
  68. 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
  69. 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
  70. Schmidt-Dannert C (2015) Biosynthesis of terpenoid natural products in fungi. Adv Biochem Eng Biotechnol 148:19–61. CrossRefPubMedGoogle Scholar
  71. Seeger R, Stijve T (1979) Amanitin content and toxicity of Amantia verna bull. Z Naturforsch 34C:330–333Google Scholar
  72. 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
  73. Tang S, Zhou Q, He Z, Luo T, Zhang P, Cai Q, Yang Z, Chen J, Chen Z (2016) Cyclopeptide toxins of lethal amanitas: compositions, distribution and phylogenetic implication. Toxicon 120:78–88. CrossRefPubMedGoogle Scholar
  74. Thongbai B, Miller SL, Stadler M, Wittstein K, Hyde KD, Lumyong S, Raspé O (2017) Study of three interesting Amanita species from Thailand: morphology, multiple-gene phylogeny and toxin analysis. PLoS One 12:e0182131. CrossRefGoogle Scholar
  75. Truong BN, Okazaki K, Fukiharu T, Takeuchi Y, Futai K, Le XT, Suzuki A (2007) Characterization of the nematocidal toxocyst in Pleurotus subgen. Coremiopleurotus. Mycoscience 48:222–230. CrossRefGoogle Scholar
  76. Tyler VE Jr, Smith AH (1963) Chromatographic detection of amanita toxins in Galerina venenata. Mycologia 55:358–359. CrossRefGoogle Scholar
  77. Tyler VE Jr, Brady LR, Benedict RG, Khana JM, Malone MH (1963) Chromatographic and pharmacologic evaluation of some toxic Galerina species. Lloydia 26:154–157Google Scholar
  78. Tyler VE Jr, Benedict RG, Brady LR, Robbers JE (1966) Occurrence of Amanita toxins in American collections of deadly amanitas. J Pharm Sci 55:590–593CrossRefGoogle Scholar
  79. Vargas N, Bernal A, Sarria V, Franco-Molano A, Restrepo S (2011) Amatoxin and phallotoxin composition in species of the genus Amanita in Colombia: a taxonomic perspective. Toxicon 58:583–590. CrossRefPubMedGoogle Scholar
  80. Varvenne D, Retornaz K, Metge P, De Haro L, Minodier P (2015) Amatoxin-containing mushroom (Lepiota brunneoincarnata) familial poisoning. Pediatr Emerg Care 31:277–288. CrossRefPubMedGoogle Scholar
  81. Walton JD (2000) Horizontal gene transfer and the evolution of secondary metabolite gene clusters in fungi: an hypothesis. Fungal Genet Biol 30:167–171. CrossRefGoogle Scholar
  82. 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
  83. Wheeler AG Jr, Krimmel BA (2015) Mirid (hemiptera: heteroptera) specialists of sticky plants: adaptations, interactions, and ecological implications. Annu Rev Entomol 60:393–414. CrossRefPubMedGoogle Scholar
  84. Wieland T (1986) Peptides of poisonous Amanita mushrooms. Springer, New YorkCrossRefGoogle Scholar
  85. Wight WD, Labuda R, Walton JD (2013) Conservation of the genes for HC-toxin biosynthesis in Alternaria jesenskae. BMC Microbiol 13:165. CrossRefPubMedPubMedCentralGoogle Scholar
  86. Wolfe BE, Richard F, Cross HB, Pringle A (2010) Distribution and abundance of the introduced ectomycorrhizal fungus Amanita phalloides in North America. New Phytol 185:803–816. CrossRefGoogle Scholar
  87. Wolfe BE, Tulloss RE, Pringle A (2012) The irreversible loss of a decomposition pathway marks the single origin of an ectomycorrhizal symbiosis. PLoS One 7:e39597. CrossRefPubMedPubMedCentralGoogle Scholar
  88. Xue JH, Wu P, Chi YL, Xu LX, Wei XY (2011) Cyclopeptides from Amanita exitialis. Nat Prod Bioprospect 1:52–66CrossRefGoogle Scholar
  89. Yarze JC, Tulloss RE (2012) Acute liver injury and renal failure due to poisonous mushroom ingestion. Am J Gastroenterol 107:790–791. CrossRefPubMedGoogle Scholar
  90. Yilmaz I, Kaya E, Sinirlioglu ZA, Bayram R, Surmen MG, Colakoglu S (2014) Clinical importance of toxin concentration in Amanita verna mushroom. Toxicon 87:68–75. CrossRefPubMedGoogle Scholar
  91. Yin W, Yang ZR (1993) A clinical analysis of twelve patients with Galerina autumnalis poisoning. Zhonghua Nei Ke Za Zhi 32:812–812Google Scholar
  92. Yocum RR, Simons DM (1977) Amatoxins and phallotoxins in Amanita species of the northeastern United States. Lloydia 40:178–190PubMedGoogle Scholar
  93. Zhang P, Chen Z, Hu J, Wei B, Zhang Z, Hu W (2005) Production and characterization of Amanitin toxins from a pure culture of Amanita exitialis. FEMS Microbiol Lett 252:223–228. CrossRefPubMedGoogle 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