Yıl: 2012 Cilt: 69 Sayı: 3 Sayfa Aralığı: 169 - 178 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar

Öz:
Oksijenik fotosentetik bakteriler grubunda yer alan, sucul ve karasal çevrede çok yaygın bir yaşam alanı bulunan siyanobakteriler (Mavi-yeşil alg) farklı morfolojik yapıya sahiptirler. Siyanobakteriler, bir kısmı oldukça etkili toksin olan ribozomal olmayan peptidler, poliketidler ve alkoloidleri içeren biyoaktif sekonder metabolit üretebilmektedirler. Toksik siyanobakterilerin yaygın bir şekilde bulunması insan ve hayvan sağlığı için risk oluşturmaktadır. Siyanobakterial toksinler veya siyanotoksinler insanlarda karaciğer kanseri, dermal kontakt irritasyonlar, gastroenterit gibi hastalıklara sebep olmaktadır. Siyanotoksinler nörotoksinler,hepatotoksinler, sitotoksinler ve dermatotoksinler olmak üzere dört ana sınıfa ayrılırlar. Fakat yapısal olarak birbirlerinden oldukça farklıdırlar. Geçtiğimiz on yıl içerisinde dört temel siyanotoksinin: mikrosistin, nodularin, saksitoksin ve silindrospermopsin biyosentez yolakları biyokimyasal ve genetik olarak tanımlanmıştır. Mikrosistinlerin, insan ve hayvan intoksikasyonlarını içeren birçok vakadan sorumlu olduğu gösterilmiştir. Bu derleme ile mikrosistinin biyosentez yolaklarını, kimyasal, genetik ve toksikolojik özelliklerin açıklanmaya çalışılmıştır.
Anahtar Kelime:

Konular: Biyoloji

The Regulation of Microcystin Biosynthesis Pathways and Genetic Mechanisms

Öz:
The cyanobacteria (blue-green algae), as they are commonly named, comprise a diverse group of oxygenic photosynthetic bacteria that inhabit a wide range of aquatic and terrestrial environments, and display incredible morphological diversity. Cyanobacteria produce bioactive secondary metabolites, including alkaloids, polyketides and non-ribosomal peptides, some of which are potent toxins. The common occurrence of toxic cyanobacteria causes problems for health of animals and human. Cyanobacterial toxins or cyanotoxins are responsible diseases such as liver cancer, dermal contact irritations and gastroenteritis in humans. The cyanotoxins divide four major classes: the neurotoxins, hepatotoxins, cytotoxins, and dermatoxins. However, this toxins are quite variety. The biosynthesis pathways of the four major cyanotoxins: microcystin, saxitoxin, nodularin and cylindrospermopsin, have been interpreted as biochemical and genetical in the past decade. Microcystins have been implicated in several cases of animal and human intoxications. This review summarizes biosynthesis pathways of microcystin, chemistry, genetic and toxicology.
Anahtar Kelime:

Konular: Biyoloji
Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık
  • 1. Bull AT, Ward AC, Goodfellow M. Search and discovery strategies for biotechnology: the paradigm shift. Microbiol Mol Biol Rev, 2000; 64(3): 573-606.
  • 2.Pilotto L, Hobson P, Burch MD, Ranmuthugala G, Attewell R, Weightman W. Acute skin irritant effects of cyanobacteria (blue-green algae) in healthy volunteers. Aust N Z J Public Health, 2004; 28(3): 220-4.
  • 3.Botes D, Wessels P, Kruger H, Runnegar M, Santikarn S, Smith R, Barna J, Williams D. Structural studies on cyanoginosins-LR, -YR, -YA, and -YM, peptide toxins from Microcystis aeruginosa. J Chem Soc, 1985; 1: 2747–2748.
  • 4.Pearson L, Mihali T, Moffitt M, Kellmann R, Neilan B. On the chemistry, toxicology and genetics of the cyanobacterial toxins, microcystin, nodularin, saxitoxin and cylindrospermopsin. Mar Drugs, 2010; 8(5):1650-80.
  • 5. Moore RE, Chen JL, Moore BS, Patterson GML, Carmichael WW. Biosynthesis of microcystin-LR. Origin of carbons in the Adda and Masp units. J Am Chem Soc, 1991; 113: 5083–4.
  • 6. Welker M, Von Dohren H. Cyanobacterial peptides nature's own combinatorial biosynthesis. FEMS Microbiol Rev, 2006; 30: 530–63.
  • 7.Ziegler K, Diener A, Herpin C, Richter R, Deutzmann R, Lockau W. Molecular characterization of cyanophycin synthetase, the enzyme catalyzing the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin). Eur J Biochem, 1998; 254: 154–9.
  • 8.Jochimsen EM, Carmichael WW, An JS, Cardo DM, Cookson ST, Holmes CE, Antunes MB, de Melo Filho DA, Lyra TM, Barreto VS, Azevedo SM, Jarvis WR. Liver failure and death after exposure to microcystins at a hemodialysis center in Brazil. N Engl J Med, 1998; 338: 873–8.
  • 9.Grosse Y, Baan R, Straif K, Secretan B, El Ghissassi F, Cogliano V. Carcinogenicity of nitrate, nitrite, and cyanobacterial peptide toxins. Lancet Oncol, 2006 ; 7(8): 628-9.
  • 10. Azevedo SM, Carmichael WW, Jochimsen EM, Rinehart KL, Lau S, Shaw GR, EagleshamGK.Human intoxication by microcystins during renal dialysis treatment in Caruaru-Brazil, Toxicol, 2002; 27:181- 182: 441-6.
  • 11.12.Gürbüz F, Metcalf JS, Karahan AG, Codd GA. Analysis of dissolved microcystins in surface water samples from Kovada Lake, Turkey. Sci Total Environ, 2009; 15: 407(13): 4038-46.
  • DeVries SE, Galey FD, Namikoshi M, Woo JC. Clinical and pathologic findings of blue-green algae (Microcystis aeruginosa) intoxication in a dog. J Vet Diagn Invest, 1993; 5(3): 403-8.
  • 13. Puschner B, Galey FD, Johnson B, Dickie CW, Vondy M, Francis T, Holstege DM. Blue-green algae toxicosis in cattle. J Am Vet Med Assoc, 1998; 1;213(11): 1605-7.
  • 14. 14. Frazier K, Colvin B, Styer E, Hullinger G, Garcia R. Microcystin toxicosis in cattle due to overgrowth of blue-green algae. Vet Hum Toxicol, 1998; 40(1): 23-4.
  • 15. Fitzgerald SD, Poppenga RH. Toxicosis dueto microcystin hepatotoxins in three Holstein heifers. J Vet Diagn Invest, 1993; 5(4): 651-3.
  • 16. Kerr LA, McCoy CP, Eaves D. Blue-green algae toxicosis in five dairy cows. J Am Vet Med Assoc, 1987; 1:191(7): 829-30.
  • 17. Short SB, Edwards WC. Blue-green algae toxicoses in Oklahoma. Vet Hum Toxicol, 1990; 32(6): 558-60.
  • 18. Galey FD, Beasley VR, Carmichael WW, Kleppe G, Hooser SB, Haschek WM. Blue-green algae (Microcystis aeruginosa) hepatotoxicosis in dairy cows. Am J Vet Res, 1987; 48(9): 1415-20.
  • 19. Dillenberg HO, Dehnel MK. Toxic waterbloom in Saskatchewan, 1959. Can Med Assoc J, 1960; 83(22): 1151-4.
  • 20.Senior VE. Algal poisoning in Saskatchewan. Can J Comp Med Vet Sci, 1960; 24(1): 26-31.
  • 21. Carbis CR, Mitchell GF, Anderson JW, McCauley I. The effects of microcystins on the serum biochemistry of carp, Cyprinus carpio L., when the toxins are administered by gavage, immersion and intraperitoneal routes. J Fish Diseas, 1996; 19(2): 151-9.
  • 22.Li XY, Chung IK, Kim JI, Lee JA. Subchronic oral toxicity of microcystin in common carp (Cyprinus carpio L.) exposed to Microcystis under laboratory conditions. Toxicon, 2004; 15: 44(8): 821-7.
  • 23. Fischer WJ, Dietrich DR. Pathological and biochemical characterization of microcystin- induced hepatopancreas and kidney damage in carp (Cyprinus carpio). Toxicol Appl Pharmacol, 2000; 164(1): 73-81.
  • 24. Tencalla FG, Dietrich DR, Schlatter C, Toxicity of Microcystis aeruginosa peptide toxin to yearling rainbow trout (Oncorhynchus mykiss). Aquat Toxicol, 1994; 30(3): 215-24.
  • 25. Ibelings BW, Bruning K, de Jonge J, Wolfstein K, Pires LM, Postma J, Burger T. Distribution of microcystins in a lake foodweb: No evidence for biomagnification. Microb Ecol, 2005; 49(4): 487-500.
  • 26.Runnegar MT, Gerdes RG, Falconer IR. The uptake of the cyanobacterial hepatotoxin microcystin by isolated rat hepatocytes. Toxicon, 1991; 29: 43–51.
  • 27. Runnegar M, Berndt N, Kaplowitz N. Microcystin uptake and inhibition of protein phosphatases: effects of chemoprotectants and self-inhibition in relation to known hepatic transporters. Toxicol Appl Pharmacol, 1995; 134: 264–72.
  • 28. Dawson RM. The toxicology of microcystins. Toxicon, 1998; 36: 953–62.
  • 29. Eriksson JE, Toivola D, Meriluoto JA, Karaki H, Han YG, Hartshorne D. Hepatocyte deformation induced by cyanobacterial toxins reflects inhibition of protein phosphatases. Biochem Biophys Res Commun, 1990; 173: 1347–53.
  • 30.Sahin A, Tencalla FG, Dietrich DR, Mez K, Naegeli H. Enzymatic analysis of liver samples from rainbow trout for diagnosis of blue-green algae-induced toxicosis. Am J Vet Res, 1995; 56: 1110–5.
  • 31. Krishnamurthy T, Carmichael WW, Sarver EW. Toxic peptides from freshwater cyanobacteria (blue-green algae). I. Isolation, purification and characterization of peptides from Microcystis aeruginosa and Anabaena flos-aquae. Toxicon, 1986; 24: 865–73.
  • 32.Dittmann E, Börner T.Genetic contributions to the risk assessment of microcystin in the environment. Toxicol Appl Pharmacol, 2005; 203(3):192-200.
  • 33.Yoshizawa S, Matsushima R, Watanabe MF, Harada K, Ichihara A, Carmichael WW, Fujiki H. Inhibition of protein phosphatases by microcystins and nodularin associated with hepatotoxicity. J Cancer Res Clin Oncol, 1990; 116: 609–14.
  • 34. Nishiwaki S, Fujiki H, Suganuma M, Nishiwaki- Matsushima R, Sugimura T. Rapid purification of protein phosphatase 2A from mouse brain by microcystin-affinity chromatography. FEBS Lett, 1991; 279: 115–8.
  • 35. Falconer IR. Tumor promotion and liver injury caused by oral consumption of cyanobacteria. Environ Toxicol Water Qual, 1991; 6: 177–84.
  • 36. Nishiwaki-Matsushima R, Ohta T, Nishiwaki S, Suganuma M, Kohyama K, Ishikawa T, Carmichael WW, Fujiki H. Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin- LR. J Cancer Res Clin Oncol, 1992; 118: 420–4.
  • 37. Yu S. Primary prevention of hepatocellular carcinoma. J Gastroenterol Hepatol, 1995; 10: 674–82.
  • 38.Tanabe Y, Sano T, Kasai F, Watanabe MM. Recombination, cryptic clades and neutral molecular divergence of the microcystin synthetase (mcy) genes of toxic cyanobacterium Microcystis aeruginosa. BMC Evol Biol, 2009; 9:115.
  • 39.Tillett D, Dittmann E, Erhard M, von Dohren H, Borner T, Neilan BA. Structural organization of microcystin biosynthesis in Microcystis aeruginosa PCC7806: an integrated peptide-polyketide synthetase system. Chem Biol, 2000; 7: 753–64.
  • 40. Christiansen G, Fastner J, Erhard M, Borner T, Dittmann E. Microcystin biosynthesis in planktothrix: genes, evolution, and manipulation. J Bacteriol, 2003; 185: 564–72.
  • 41.Rouhiainen L, Vakkilainen T, Siemer BL, Buikema W, Haselkorn R, Sivonen K. Genes coding for hepatotoxic heptapeptides (microcystins) in the cyanobacterium Anabaena strain 90. Appl Environ Microbiol, 2004; 70: 686–92.
  • 42.Hicks LM, Moffitt MC, Beer LL, Moore B, Kelleher NL. Structural characterisation of in vitro and in vivo intermediates on the loading module of microcystin synthetase. ACS Chem Biol, 2006; 1: 93–102.
  • 43. Nishizawa T, Asayama M, Shirai M. Cyclic heptapeptide microcystin biosynthesis requires the glutamate racemase gene. Microbiology, 2001; 147: 1235–41.
  • 44. Sielaff H, Dittmann E, Tandeau De Marsac N, Bouchier C, Von Dohren H, Borner T, Schwecke T. The mcyF gene of the microcystin biosynthetic gene cluster from Microcystis aeruginosa encodes an aspartate racemase. Biochem J, 2003; 373: 909–16.
  • 45. Pearson LA. Barrow KD, Neilan BA. Characterization of the 2-hydroxy-acid dehydrogenase McyI, encoded within the microcystin biosynthesis gene cluster of Microcystis aeruginosa PCC7806. J Biol Chem, 2007; 282: 4681–92.
  • 46.Pearson LA, Hisbergues M, Borner T, Dittmann E, Neilan BA. Inactivation of an ABC transporter gene, mcyH, results in loss of microcystin production in the cyanobacterium Microcystis aeruginosa PCC 7806. Appl Environ Microbiol, 2004; 70: 6370–8.
  • 47. Shi L, Carmichael WW, Miller I. Immuno-gold localization of hepatotoxins in cyanobacterial cells. Arch Microbiol, 1995; 16: 7–15.
  • 48. Young FM, Thomson C, Metcalf JS, Lucocq JM, Codd GA. Immunogold localisation of microcystins in cryosectioned cells of Microcystis. J Struct Biol, 2005; 151: 208–14.
  • 49. Kaebernick M, Neilan BA, Borner T, Dittmann E. Light and the transcriptional response of the microcystin biosynthesis gene cluster. Appl Environ Microbiol, 2000; 66: 3387–92.
  • 50. Mikalsen B, Boison G, Skulberg OM, Fastner J, Davies W, Gabrielsen TM, Rudi K, Jakobsen KS. Natural variation in the microcystin synthetase operon mcyABC and impact on microcystin production in Microcystis strains. J Bacteriol, 2003; 185: 2774–85.
  • 51.Tooming-Klunderud A, Mikalsen B, Kristensen T, Jakobsen KS. The mosaic structure of the mcyABC operon in Microcystis. Microbiology, 2008; 154: 1886–99.
  • 52. Sivonen K. Effects of light, temperature, nitrate, orthophosphate, and bacteria on growth of and hepatotoxin production by Oscillatoria agardhii strains. Appl Environ Microbiol, 1990; 56: 2658–66.
  • 53. Lukac M, Aegerter R. Influence of trace metals on growth and toxin production of Microcystis aeruginosa. Toxicon, 1993; 31: 293–305.
  • 54. Van der Westhuizen AJ, Eloff JN. Effect of temperature and light on the toxicity and growth of the blue-green alga Microcystis aeruginosa (UV- 006). Planta, 1985; 163: 55–9.
  • 55.56.Song L, Sano T, Li R, Watanabe M, Liu Y, Kaya K. Microcystin production of Microcystis viridis (cyanobacteria) under different culture conditions. Phycol Res, 1998; 42: 19.
  • Davis TW, Berry DL, Boyer GL, Gobler CJ. The effects of temperature and nutrients on the growth and dynamics of toxic and non-toxic strains of Microcystis during cyanobacteria blooms. Harmful Algae, 2009; 8 : 715–25.
  • 57.Tonk L, Visser PM, Christiansen G, Dittmann E, Snelder EO, Wiedner C, Mur LR, Huisman J. The microcystin composition of the cyanobacterium Planktothrix agardhii changes toward a more toxic variant with increasing light intensity. Appl Environ Microbiol, 2005; 71: 5177–81.
  • 58. Sevilla E, Martin-Luna B, Vela L, Bes MT, Fillat MF, Peleato ML. Iron availability affects mcyD expression and microcystin-LR synthesis in Microcystis aeruginosa PCC7806. Environ Microbiol, 2008; 10: 2476–83.
  • 59. Kaebernick M, Dittmann E, Borner T, Neilan BA. Multiple alternate transcripts direct the biosynthesis of microcystin, a cyanobacterial nonribosomal peptide. Appl Environ Microbiol, 2002; 68: 449–55.
  • 60. Meissner K, Dittmann E, Borner T. Toxic and non- toxic strains of the cyanobacterium Microcystis aeruginosa contain sequences homologous to peptide synthetase genes. FEMS Microbiol Lett, 1996;135: 295–303.
  • 61. Dittmann E, Meissner K, Borner T. Conserved sequences of peptide synthetase genes in the cyanobacterium Microcystis aeruginosa. Phycologia, 1996; 35: 62–7.
  • 62. Neilan BA, Dittmann E, Rouhiainen L, Bass RA, Schaub V, Sivonen K, Borner T. Nonribosomal peptide synthesis and toxigenicity of cyanobacteria. J Bacteriol, 1999; 181: 4089–97.
  • 63. Kurmayer R, Kutzenberger T. Application of real- time PCR for quantification of microcystin genotypes in a population of the toxic cyanobacterium Microcystis sp. Appl Environ Microbiol, 2003; 69: 6723–30.
  • 64. Kurmayer R, Dittmann E, Fastner J, Chorus I. Diversity of microcystin genes within a population of the toxic cyanobacterium Microcystis spp. in Lake Wannsee (Berlin, Germany). Microb Ecol, 2002; 43: 107–8.
  • 65.Zhang Z, Zhang XX, Qin W, Xu L, Wang T, Cheng S, Yang L. Effects of microcystin-LR exposure on matrix metalloproteinase-2/-9 expressionand cancer cell migration. Ecotoxicol Environ Saf, 2012; 77: 88-93.
  • 66. Xu L, Qin W, Zhang H, Wang Y, Dou H, Yu D, Ding Y, Yang L, Wang Y. Alterations in microRNA expression linked to microcystin-LR-induced tumorigenicity in human WRL-68 Cells. Mutat Res, 2012; 18: 743(1-2): 75-82.
  • 67.Zhao S, Xie P, Li G, Jun C, Cai Y, Xiong Q, Zhao Y.The proteomic study on cellular responses of the testes of zebrafish (Danio rerio) exposed to microcystin-RR. Proteomics, 2012; 12(2): 300-12.
  • 68. Srivastava A, Choi GG, Ahn CY, Oh HM, Ravi AK, Asthana RK. Dynamics of microcystin production and quantification of potentially toxigenic Microcystis sp. using real-time PCR. Water Res, 2012; 1: 46(3): 817-27.
  • 69. Cantor GH, Beckonert O, Bollard ME, Keun HC, Ebbels TM, Antti H, Wijsman JA, Bible RH, Breau AP, Cockerell GL, Holmes E, Lindon JC, Nicholson JK. Integrated histopathological and urinary metabonomic investigation of the pathogenesis of Microcystin-LR toxicosis. Vet Pathol, 2012; in press.
APA YALÇIN AZARKAN S (2012). Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar. , 169 - 178.
Chicago YALÇIN AZARKAN SERAP Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar. (2012): 169 - 178.
MLA YALÇIN AZARKAN SERAP Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar. , 2012, ss.169 - 178.
AMA YALÇIN AZARKAN S Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar. . 2012; 169 - 178.
Vancouver YALÇIN AZARKAN S Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar. . 2012; 169 - 178.
IEEE YALÇIN AZARKAN S "Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar." , ss.169 - 178, 2012.
ISNAD YALÇIN AZARKAN, SERAP. "Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar". (2012), 169-178.
APA YALÇIN AZARKAN S (2012). Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar. Türk Hijyen ve Deneysel Biyoloji Dergisi, 69(3), 169 - 178.
Chicago YALÇIN AZARKAN SERAP Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar. Türk Hijyen ve Deneysel Biyoloji Dergisi 69, no.3 (2012): 169 - 178.
MLA YALÇIN AZARKAN SERAP Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar. Türk Hijyen ve Deneysel Biyoloji Dergisi, vol.69, no.3, 2012, ss.169 - 178.
AMA YALÇIN AZARKAN S Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar. Türk Hijyen ve Deneysel Biyoloji Dergisi. 2012; 69(3): 169 - 178.
Vancouver YALÇIN AZARKAN S Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar. Türk Hijyen ve Deneysel Biyoloji Dergisi. 2012; 69(3): 169 - 178.
IEEE YALÇIN AZARKAN S "Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar." Türk Hijyen ve Deneysel Biyoloji Dergisi, 69, ss.169 - 178, 2012.
ISNAD YALÇIN AZARKAN, SERAP. "Mikrosistin Biyosentez Yolaklarının Düzenlenmesi and Genetik Mekanizmalar". Türk Hijyen ve Deneysel Biyoloji Dergisi 69/3 (2012), 169-178.