The genetics and genomics of cyanobacterial toxicity

  • Brett A Neilan
  • LA Pearson
  • MC Moffitt
  • KT Mihali
  • M Kaebernick
  • R Kellmann
  • F Pomati
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 619)


Microcystis Aeruginosa Paralytic Shellfish Poisoning Paralytic Shellfish Adenylation Domain Microcystin Production 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Banker R, Carmeli S, Hadas O, Teltsch B, Porat R, Sukenik A (1997) Identification of cylindrospermopsin in Aphanizomenon ovalisporum (Cyanophyceae) isolated from lake Kinneret, Israel. J Phycol 33:613–6CrossRefGoogle Scholar
  2. Beltran EC, Neilan BA (2000) Geographical segregation of the neurotoxin–producing cyanobacterium Anabaena circinalis. Appl Environ Microbiol 66:4468–74PubMedCrossRefGoogle Scholar
  3. Bowling LC (1994) Occurrence and possible causes of a severe cyanobacterial bloom in Lake Cargelligo, New South Wales. Aust J Mar Freshwater Res 45:737–45CrossRefGoogle Scholar
  4. Bowling LC, Baker PD (1996) Major cyanobacterial bloom in the Barwon–Darling River, Australia, in 1991, and underlying limnological conditions. Mar Freshwater Res 47:643–57CrossRefGoogle Scholar
  5. Burgoyne DL, Hemscheidt TK, Moore RE, Runnegar MTC (2000) Biosynthesis of cylindrospermopsin. J Org Chem 65:152–6PubMedCrossRefGoogle Scholar
  6. Carmichael WW (1992) Cyanobacteria secondary metabolites– the cyanotoxins. J Appl Bacteriol 72:445–59PubMedGoogle Scholar
  7. Castro D, Vera D, Lagos N, Garcia C, Vasquez M (2004) The effect of temperature on growth and production of paralytic shellfish poisoning toxins by the cyanobacterium Cylindrospermopsis raciborskii C10. Toxicon 44:483–9PubMedCrossRefGoogle Scholar
  8. Christiansen G, Fastner J, Erhard M, Borner T, Dittmann E (2003) Microcystin biosynthesis in planktothrix: genes, evolution, and manipulation. J Bacteriol 185(2):564–72PubMedCrossRefGoogle Scholar
  9. Dittmann E, Erhard M, Kaebernick M, Scheler C, Neilan BA, von Dohren H, Borner T (2001) Altered expression of two light–dependent genes in a microcystin–lacking mutant of Microcystis aeruginosa PCC 7806. Microbiol 147(11):3113–9Google Scholar
  10. Dittmann E, Neilan BA, Erhard M, von Dohren H, Borner T (1997) Insertional mutagenesis of a peptide synthetase gene that is responsible for hepatotoxin production in the cyanobacterium Microcystis aeruginosa PCC 7806. Mol Microbiol 26(4):779–87PubMedCrossRefGoogle Scholar
  11. Downing TG, Sember C, Gehringer MM, Leukes W (2005) Medium N:P ratios and specific growth rate co–modulate microcystin and protein content in Microcystis aeruginosa PCC7806 and M. aeruginosa UV027. Microbial Ecol 49:1–6CrossRefGoogle Scholar
  12. Eisen JA Fraser CM (2003) Phylogenomics: intersection of evolution and genomics. Science 300, 1706–1707PubMedCrossRefGoogle Scholar
  13. Gallon JR, Chit KN, Brown EG (1990) Biosynthesis of the tropane–related cyanobacterial toxin Anatoxin–a: Role of ornithine decarboxylase: Phytochem 29:1107–1111Google Scholar
  14. Gallon JR, Kittakoop P, Brown EG (1994) biosynthesis of anatoxin–a by Anabaena flos–aquae: examination of primary enzymatic steps: Phytochem 35:1195–203Google Scholar
  15. Gupta N, BASB, LR (2002) Growth characteristics and toxin production in batch cultures of Anabaena flos–aquae: effects of culture media and duration. World J Microbiol Biotech 18:29–35CrossRefGoogle Scholar
  16. Harada K, Ohtani I, Iwamoto K, Suzuki M, Watanabe MF, Watanabe M, Terao K (1994) Isolation of cylindrospermopsin from a cyanobacterium Umezakia natans and its screening method. Toxicon 32:73–84PubMedCrossRefGoogle Scholar
  17. Hemscheidt T, Burgoyne DL, Moore RE (1995a) Biosynthesis of anatoxin–a(s). (2S,4S)–4–hydroxyarginine as an intermediate. J Chem Soc, Chem Comm 205–6Google Scholar
  18. Hemscheidt T, Rapala J, Sivonen K, Skulberg OM (1995b) Biosynthesis of anatoxin–a in Anabaena flos–aquae and homoanatoxin–a in Oscillatoria formosa. J Chem Soc, Chem Comm 1361–2Google Scholar
  19. Horikoshi K (1991) Microorganisms in alkaline environments. VCH, New York, pp 110Google Scholar
  20. Kaebernick M, Neilan BA, Borner T, Dittmann E (2000) Light and the transcriptional response of the microcystin biosynthesis gene cluster. Appl Environ Microbiol 66(8):3387–92PubMedCrossRefGoogle Scholar
  21. Kleinkauf H, Von Dohren H (1996) A nonribosomal system of peptide biosynthesis. Eur J Biochem 236(2):335–51PubMedCrossRefGoogle Scholar
  22. Jones GJ, Negri AP (1997) Persistence and degradation of cyanobacterial paralytic shellfish poisons (PSPs) in freshwaters. Water Res 31:525–33CrossRefGoogle Scholar
  23. Kellmann R, Mills T, Neilan BA (2005) Functional modelling and phylogenetic distribution of putative cylindrospermopsin biosynthesis genes. J Mol Evol 61:1–5CrossRefGoogle Scholar
  24. Lehtimöki J, Moisander P, Sivonen K, Kononen K (1997) Growth, nitrogen fixation, and nodularin production by two Baltic Sea cyanobacteria. Appl Environ Microbiol 63:1647–56Google Scholar
  25. Li RH, Carmichael WW, Brittain S, Eaglesham GK, Shaw GR, Liu YD, Watanabe MM (2001) First report of the cyanotoxins cylindrospermopsin and deoxycylindrospermopsin from Raphidiopsis curvata (cyanobacteria). J Phycol 37:1121–6CrossRefGoogle Scholar
  26. Long BM, Jones GJ, Orr PT (2001) Cellular microcystin content in N–limited Microcystis aeruginosa can be predicted from growth rate. Appl Environ Microbiol 67(1):278–83PubMedCrossRefGoogle Scholar
  27. Lukac M, Aegerter R (1993) Influence of trace metals on growth and toxin production of Microcystis aeruginosa. Toxicon 31(3):293–305PubMedCrossRefGoogle Scholar
  28. Luukkainen R, Sivonen K, Namikoshi M, Fardig M, Rinehart KL, Niemela SI (1995) Isolation and identification of eight microcystins from thirteen Oscillatoria agardhii strains and structure of a new microcystin. Appl Environ Microbiol 59(7):2204–9Google Scholar
  29. Maestri O, Joset F (2000) Regulation by external pH and stationary growth phase of the acetolactate synthase from Synechocystis PCC6803. Mol Microbiol 37:828–38PubMedCrossRefGoogle Scholar
  30. Mikalsen B, Boison G, Skulberg OM, Fastner J, Davies W, Gabrielsen TM, Rudi K, Jakobsen KS (2003) Natural variation in the microcystin synthetase operon mcyABC and impact on microcystin production in Microcystis strains. J Bacteriol 185(9):2774–85PubMedCrossRefGoogle Scholar
  31. Moffitt MC (2003) Non–ribosomal biosynthesis of the cyanobacterial toxin nodularin. PhD thesis UNSWGoogle Scholar
  32. Moffitt MC, Neilan BA (2004) Characterization of the nodularin synthetase gene cluster and proposed theory of the evolution of cyanobacterial hepatotoxins. Appl Environ Microbiol 70(11):6353–62PubMedCrossRefGoogle Scholar
  33. Moore RE, Chen JL, Moore BS, Patterson GML, Carmichael WW (1991) Biosynthesis of Microcystin–LR. Origin of the carbons in the Adda and Masp units. J Am Chem Soc 113:5083–4CrossRefGoogle Scholar
  34. Moore BS, Ohtani I, d KCB, Moore RE, Carmichael WW (1992) Biosynthesis of anatoxin–a(s): origin of the carbons: Tetrahed. Lett 33:6595–8Google Scholar
  35. Namikoshi M, Murakami T, Fujiwara T, Nagai H, Niki T, Harigaya E, Watanabe MF, Oda T, Yamada J, Tsujimura S (2004) Biosynthesis and transformation of homoanatoxin–a in the cyanobacterium Raphidiopsis mediterranea Skuja and structures of three new homologues: Chem Res Toxicol 17:1692–6Google Scholar
  36. Negri A, Llewellyn LE, Doyle J, Webster N, Frampton D, Blackburn S (2003) Paralytic shellfish toxins are restricted to few species among Australia’s taxonomic diversity of cultured microalgae. J Phycol 39:663–667CrossRefGoogle Scholar
  37. Negri AP, Jones GJ, Blackburn SI, Oshima Y, Onodera H (1997) Effect of culture and bloom development and of sample storage on paralytic shellfish poisons in the cyanobacterium Anabaena circinalis. J Phycol 33:26–35CrossRefGoogle Scholar
  38. Neilan BA, Saker ML, Fastner J, Torokne A, Burns BP (2003) Phylogeography of the invasive cyanobacterium Cylindrospermopsis raciborskii. Mol Ecol 12:133–140PubMedCrossRefGoogle Scholar
  39. Nishizawa T, Asayama M, Shirai M (2001) Cyclic heptapeptide microcystin biosynthesis requires the glutamate racemase gene. Microbiol147(5):1235–41Google Scholar
  40. Nogueira IC, Saker ML, Pflugmacher S, Wiegand C, Vasconcelos VM (2004) Toxicity of the cyanobacterium Cylindrospermopsis raciborskii to Daphnia magna. Environ Toxicol 19:453–9PubMedCrossRefGoogle Scholar
  41. Onodera H, Satake M, Oshima Y, Yasumoto T, Carmichawel WW (1997) New saxitoxin analogues from the freshwater filamentous cyanobacterium Lyngbya wollei. Nat Toxins 5:146–51PubMedGoogle Scholar
  42. Ohtani I, Moore RE, Runnegar MTC (1992) Cylindrospermopsin – a potent hepatotoxin from the blue–green– alga Cylindrospermopsis raciborskii. J Am Chem Soc 114:7941–7942CrossRefGoogle Scholar
  43. Orr PT, Jones GJ (1998) Relationship between microcystin production and cell division rates in nitrogen–limited Microcystis aeruginosa cultures. Limnol Oceanog 43(7):1604–1614Google Scholar
  44. Oshima Y (1995) Chemical and enzymatic transformation of paralytic shellfish toxins in marine organisms. In: Harmful Algal Blooms. Lassus P, Arzul G, Erard E, Gentien P, Marcaillou C (eds), Lavoisier, Paris, pp 475–480Google Scholar
  45. Pearson LA, Hisbergues M, Borner T, Dittmann E, Neilan BA (2004) Inactivation of an ABC transporter gene, mcyH, results in loss of microcystin production in the cyanobacterium Microcystis aeruginosa PCC 7806. Appl Environ Microbiol 70(11):6370–8PubMedCrossRefGoogle Scholar
  46. Pomati F, Neilan BA (2004) PCR–based positive hybridisations to detect genomic diversity associated with bacterial secondary metabolism. Nucleic Acid Res 32(1):e7Google Scholar
  47. Pomati F, Neilan BA, Manarolla G, Suzuki T, Rossetti C (2003a) Enhancement of intracellular saxitoxin accumulation by lidocaine hydrochloride in the cyanobacterium Cylindrospermopsis raciborskii T3 (Nostocales). J Phycol 39:535–42CrossRefGoogle Scholar
  48. Pomati F., B. P. Burns and B. A. Neilan (2004a) Identification of a Na+ dependent transporter associated with saxitoxin production in the cyanobacterium Anabaena circinalis. Appl Environ Microbiol 70:4711–9CrossRefGoogle Scholar
  49. Pomati F, Rossetti C, Manarolla G, Burns BP, Neilan BA (2004b) Interaction between Intracellular Na+ levels and saxitoxin production in Cylindrospermopsis raciborskii T3. Microbiol 150:455–61CrossRefGoogle Scholar
  50. Pomati F, Rossetti C, Calamari D, Neilan BA (2003b) Effects of saxitoxin and veratridine on bacterial Na+–K+ fluxes: a prokaryotic–based saxitoxin bioassay. Appl Environ Microbiol 69:7371–6CrossRefGoogle Scholar
  51. Rantala A, Fewer DP, Hisbergues M, Rouhiainen L, Vaitomaa J, Borner T, Sivonen K (2004) Phylogenetic evidence for the early evolution of microcystin synthesis. Proc Natl Acad Sci USA 101(2):568–73Google Scholar
  52. Rapala J, Sivonen K, Luukkainen R, Niemelö SI (1993) Anatoxin–a concentration in Anabaena and Aphanizomenon at different environmental conditions and comparison of growth by toxic and non–toxic Anabaena strains, a laboratory study. J App Phycol 5:581–91CrossRefGoogle Scholar
  53. Rohrlack T, Dittmann E, Henning M, Borner T, Kohl JG (1999) Role of microcystins in poisoning and food ingestion inhibition of Daphnia galeata caused by the cyanobacterium Microcystis aeruginosa. Appl Environ Microbiol 65(2):737–9PubMedGoogle Scholar
  54. Rouhiainen L, Vakkilainen T, Siemer BL, Buikema W, Haselkorn R, Sivonen K (2004) Genes coding for hepatotoxic heptapeptides (microcystins) in the cyanobacterium Anabaena strain 90. Appl Environ Microbiol 70(2):686–92PubMedCrossRefGoogle Scholar
  55. Saker ML, Neilan BA (2001) Varied diazotrophies, morphologies, and toxicities of genetically similar isolates of Cylindrospermopsis raciborskii (Nostocales, Cyanophyceae) from northern Australia. Appl Environ Microbiol 67:1839–45PubMedCrossRefGoogle Scholar
  56. Sako Y, Yoshida T, Uchida A, Arakawa O, Noguchi T, Ishida Y (2001) Purification and characterization of a sulfotransferase specific to N–21 of saxitoxin and gonyautoxin 2+3 from the toxic dinoflagellate Gymnodinium catenatum (Dinophyceae). J Phycol 37:1044–51CrossRefGoogle Scholar
  57. Schantz EJ, Ghazarossian VE, Schnoes FM, Strong JP, Springer JD, Pezzanite JD, Clardy J (1975) The structure of saxitoxin. J Am Chem Soc 97:1238–9PubMedCrossRefGoogle Scholar
  58. Schembri MA, Neilan BA, Saint CP (2001) Identification of genes implicated in toxin production in the cyanobacterium Cylindrospermopsis raciborskii. Environ Toxicol 16:413–21PubMedCrossRefGoogle Scholar
  59. Shalev–Alon G, Sukenik A, Livnah O, Schwarz R, Kaplan A (2002) A novel gene encoding amidinotransferase in the cylindrospermopsin producing cyanobacterium Aphanizomenon ovalisporum. FEMS Microbiol Lett 209:83–7CrossRefGoogle Scholar
  60. Shi L, Carmichael WW, Miller I (1995) Immunogold localization of hepatotoxins in cyanobacterial cells. Arch Microbiol 163(1):7–15PubMedCrossRefGoogle Scholar
  61. Shimizu Y (1986a) Biosynthesis and biotransformation of marine invertebrate toxins. In: Natural Toxins. Harris JB (ed) Clarendon Press, Oxford UK, pp 115–125Google Scholar
  62. Shimizu Y (1986b) Toxigenesis and biosynthesis of saxitoxin analogues. Pure Appl Chem 58:257–62CrossRefGoogle Scholar
  63. Shimizu Y (1996) Microalgal metabolites – a new perspective. Ann Rev Microbiol 50:431–65CrossRefGoogle Scholar
  64. Shimizu Y, Norte M, Hori A, Genenah A, Kobayashi M (1984) Biosynthesis of saxitoxin analogues: the unexpected pathway. J Am Chem Soc 106:6433–4CrossRefGoogle Scholar
  65. Sielaff H, Dittmann E, Tandeau De Marsac N, Bouchier C, Von Dohren H, Borner T, Schwecke T (2003) The mcyF gene of the microcystin biosynthetic gene cluster from Microcystis aeruginosa encodes an aspartate racemase. Biochem J 373(3):909–16PubMedCrossRefGoogle Scholar
  66. Sivonen K, Jones G (1999) Cyanobacterial toxins. In: Toxic Cyanobacteria in Water. Chorus I, Bartram J (eds) WHO E & FN Spon Publishers, London, pp 41–111Google Scholar
  67. Sugimoto E, Pizer LI (1968) The mechanism of end product inhibition of serine biosynthesis. I. Purification and kinetics of phosphoglycerate dehydrogenase. J Biol Chem 243(9):2081–9PubMedGoogle Scholar
  68. Tanabe Y, Kaya K, Watanabe MM (2004) Evidence for recombination in the microcystin synthetase (mcy) genes of toxic cyanobacteria Microcystis spp. J Mol Evol 58(6):633–41PubMedCrossRefGoogle Scholar
  69. Taroncher–Oldenburg G, Anderson DM (2000) Identification and characterization of three differentially expressed genes, encoding S–adenosylhomocysteine hydrolase, methionine aminopeptidase, and a histone–like protein, in the toxic dinoflagellate Alexandrium fundyense. Appl Environ Microbiol 66:2105–12PubMedCrossRefGoogle Scholar
  70. Taroncher–Oldenburg G, Kulis DM, Anderson DM (1997) Toxin variability during the cell cycle of the dinoflagellate Alexandrium fundyense. Limnol Oceanogr 42:1178–88Google Scholar
  71. Tillett D, Dittmann E, Erhard M, von Dohren H, Borner T, Neilan BA (2000) Structural organization of microcystin biosynthesis in Microcystis aeruginosa PCC7806: an integrated peptide–polyketide synthetase system. Chem Biol 7(10):753–64PubMedCrossRefGoogle Scholar
  72. Utkilen H, Gjolme N (1995) Iron–stimulated toxin production in Microcystis aeruginosa. Appl Environ Microbiol 61(2):797–800PubMedGoogle Scholar
  73. Velzeboer RMA, Baker PD, Rositano J, Heresztyn T, Codd GA, Raggett SL (2000) Geographical patterns of occurrence and composition of saxitoxins in the cyanobacterial genus Anabaena (Nostocales, Cyanophyta) in Australia. Phycologia 39:395–407CrossRefGoogle Scholar
  74. Waditee R, Hibino T, Tanaka Y, Nakamura T, Incharoensakdi A, Takabe T (2001) The halotolerant cyanobacterium Aphanothece halophytica contains an Na+/H+ antiporter, homologous to eukaryotic ones, with novel ion specificity affected by C–terminal tail. J Biol Chem 276:36931–8PubMedCrossRefGoogle Scholar
  75. Yin QQ, Carmichael WW, Evans WR (1997) Factors influencing growth and toxin production by cultures of the freshwater cyanobacterium Lyngbya wollei Farlow ex Gomont. J Appl Phycol 9:55–63CrossRefGoogle Scholar
  76. Yoshida T, Sako Y, Uchida A, Kakutani T, Arakawa O, Noguchi T, Ishida Y (2002) Purification and characterization of a sulfotransferase specific to O–22 of 11–hydroxy saxitoxin from the toxic dinoflagellate Gymnodinium catenatum (Dinophyceae). Fisheries Science 68:634–42.CrossRefGoogle Scholar
  77. Young FM, Thomson C, Metcalf SS, Lucocq JM, Codd GA (2005) Immunogold localization of microcystins in cryosectioned cells of Microcystis. J Struct Biol 151(2):208–14PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Brett A Neilan
    • 1
  • LA Pearson
    • 1
  • MC Moffitt
    • 1
  • KT Mihali
    • 1
  • M Kaebernick
    • 1
  • R Kellmann
    • 1
  • F Pomati
    • 1
  1. 1.Cyanobacteria and Astrobiology Research Laboratory School of Biotechnology and Biomolecular SciencesThe University of New South WalesSydney 2052Australia

Personalised recommendations