Abstract
Cyanobacteria produce a number of biologically active substances. In addition to their well-known alkaloid toxins (see Sivonen and Jones 1999 for an overview), these encompass peptides and depsipeptides. While approximately 60 structural variants of the hepatotoxic microcystins are already known (Sivonen and Jones 1999), the non-hepatotoxic peptides and depsipeptides have been studied to a far lesser extent. These substances have been detected irrespective of whether the object was the study of toxic or of non-toxic strains (Namikoshi and Rinehart 1996). On the other hand, evidence is increasing for biological effects of cyanobacteria which cannot be accounted for by those cyanobacterial metabolites currently understood to encompass “the cyanotoxins”. This suggests that cyanobacteria contain not only numerous metabolites whose bioactivity is poorly understood, but also further currently unknown toxins. Chapter 7.1 presents a review of peptides and depsipeptides potentially relevant as bioactive substances.
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References
Amarowicz R, Shahidi F (1994) Application of sephadex LH20 chromatography for the separation of cyanogenic glycosides and hydrophilic phenolic compounds of flexsed. J Chromatogr 17: 1291–1299
An JS, Carmichael WW (1994) Use of a colorimetric protein phosphatase inhibition assay and enzyme linked immunosorbent assay for the study of microcystins and nodularins. Toxicon 32: 1495–1507
Arai Y, Kusomoto Y, Nagao M, Shiojima K, Ageta H (1983) Yakugaku Zasshi 103:356-359 Borowitzka MA (1995) Microalgae as sources of pharmaceuticals and other biologically active compounds. J Appl Phycol 7: 3–15
Bury NR, Eddy FB, Codd GA (1995) The effects of the cyanobacterium Microcystis aeruginosa, the cyanobacterial hepatotoxin microcystin-LR, and ammonia on growth rate and ionic regulation of brown trout. J Fish Biol 46: 1042–1054
Cardellina J, Moore RE (1980) Tetrahedron 36: 993–996
Cardellina JH, Marner FJ, Moore RE (1979) Seaweed dermatitis: structure of lyngbiatoxin A. Science 204: 193–195
Carter DC, Moore RE, Mynderse JS, Niemczura WP, Todd JS (1984) Structure of majusculamide C, a cyclic depsipeptide from Lyngbya majuscula. J Org Chem 49: 236–241
Casanova MT, Burch MD, Brock MA, Bond PM (1999) Does toxic Microcystis aeruginosaaffect Aquatic plant establishment? Environ Toxicol 14 (1): 97–110
De Silva ED, Williams DE, Andersen RJ, Klix H, Holmes CFB, Allen TM (1992) Motuporin, a potent phosphatase inhibitor isolated from the Papua New Guinea sponge Theonella swinhoeiGray. Tetrahedron Lett 33: 1561–1564
Delaney JM, Wilkins RM (1995) Toxicity of microcystin-LR, isolated from Microcystis aeruginosa,against various insect species. Toxicon 33: 771–778
DeMott WR, Zhang QX, Carmichael WW (1991) Effects of toxic cyanobacteria and purified toxins on the survival and feeding of a copepod and three species of Daphnia. Limnol Oceanogr 36: 1346–1357
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 aeruginosaPCC 7806. Mol Microbiol 26: 779–787
Edwards C, Lawton LA, Coyle SM, Ross P (1996) Laboratory-scale purification of microcystins using flash chromatography and reversed-phase high-performance liquid chromatography. J Chromatogr A 734: 163–173
Elfant M, Bryant L, Starcher B (1985) Isolation and characterization of a proteinase inhibitor from marama beans (42184). Proc Soc Exp Biol Med 180: 329–333
Erhard M (1999) Matrix-assisted laser desorption/ionisation-time of flight. Massenspektrometrie von Cyanobakterien und Untersuchungen zur Biosynthese und Funktion der Microcystine. Dissertation, Technische Universitat Berlin Erhard M, von Dohren H, Jungblut P (1997) Rapid typing and elucidation of new secondary metabolites of intact cyanobacteria using MALDI-TOF mass spectrometry. Nature Biotechn 15: 906–909
Evans JNS (1995) Biomolecular NMR spectroscopy. Oxford University Press, Oxford New York Tokyo
Fastner J, Flieger I, Neumann U (1998) Optimised extraction of microcystins from field samples — a comparison of different solvents and procedures. Wat Res 32: 3177–3181
Fastner J, Heinze R, Chorus I (1995) Microcystin content, hepatotoxicity and cytotoxicity of cyanobacteria in some German water bodies. Wat Sci Technol 32: 165–170
Feuillade M, Jann-Para G, Feuillade J (1996) Toxic compounds to Artemia from- and isolates of the cyanobacterium Planktothrix rubescens. Arch Hydrobiol 138: 175–186
Fischer, WJ, Dietrich, DR (2000). Toxicity of the cyanobacterial cyclic heptapeptide toxins microcystin- LR and -RR in early life-stages of the African clawed frog (Xenopus laevis). Aquat Toxicol 49: 189–198
Forchert A (1999) Isolierung und Charakterisierung neuer Peptidstrukturen aus Cyanobakterien der Gattungen Microcystisund Planktothrixspp. Dissertation, Technische Universitat Berlin
Frankmolle WP, Knubel G, Moore RE, Patterson GML (1992) Antifungal cyclic peptides from the terrestrial blue-green alga Anabaena laxa. II. Structures of laxaphycins A, B, D and E. J Antibiot 45: 1458–1466
Frankmolle WP, Larsen LK, Caplan FR, Patterson GML, Knubel G, Levine I A, Moore RE (1991) Antifungal cyclic peptides from the terrestrial blue-green alga Anabaena laxaI. Isolation and biological properties. J Antibiot 45: 1451–1457
Frechet D, Guitton JD, Herman F, Faucher D, Helynck G, Monegier de Sorbier B, Ridoux JP, James-Surcouf E, Vuilhorgne M (1994) Solution structure of RP 71955, a new 21 amino acid tricyclic peptide active against HIV-1 virus. Biochemistry 33: 42–50
Fujii K, Harada KI, Suzuki M, Kondo F, Ikai Y, Oka H, Sivonen K (1995) Novel cyclic peptides together with microcystins produced by toxic cyanobacteria, Anabaenasp.. In: 37th Symposium on The Chemistry of Natural Products (Tokushima), Symposium Papers, Tokuschima, pp. 445–450
Fujii K, Sivonen K, Adachi K, Noguchi K, Sano H, Hirayama K, Suzuki M, Harada K (1997) Comparative study of toxic and nontoxic cyanobacterial products — novel peptides from toxic Nodularia spumigenaAVI. Tetrahedron Lett 38: 5525–5528
Fujiki H, Suganuma M, Hakii H, Bartolini G, Moore RE, Takayama S, Sugimura T (1984) A two- stage mouse skin carcinogenesis study of lyngbiatoxin A. J Cancer Res Clin Oncol 108: 174–176
Gerwick WH, Jiang ZD, Agarwal SK, Farmer BT (1992) Total structure of hormothamnin A, a toxic cyclic undecapeptide from the tropical marine cyanobacterium Hormothamnion enteromorphoides. Tetrahedron 48: 2313–2324
Gerwick WH, Mrozek CH, Moghaddam MF, Agarwal SK (1989) Novel cytotoxic peptides from the tropical marine cyanobacterium Hormothamnion enteromorphoides. 1. Discovery, isolation and initial chemical and biological characterization of the hormothamnins from wild and cultured material. Experientia 45: 115–121
Gerwick WH, Roberts MA, Proteau PJ, Chen JL (1994) Screening cultured marine microalgae for anticancer-type activity. J Appl Phycol 6: 143–149
Golakoti T, Ogino J, Hetzel CE, Husebo TL, Jensen CM, Larsen KL, Patterson GML, Moore RE, Mooberry SL, Corbett TH, Valeriote FA (1995) Structure determination, conformational analysis, chemical stability studies, and antitumor evaluation of the cryptophycins. Isolation of 18 new analogs from Nostocsp. strain GSV 224. J Am Chem Soc 117: 12030–12049
Gregson JM, Chen JL, Patterson GML, Moore RE (1992) Structures of puwainaphycins A-E. Tetrahedron 48: 3727–3734
Haney JF, Sasner JJ, Ikawa M (1995) Effects of products released by Aphanizomenon flos-aquaeand purified saxitoxin on the movements of Daphnia carinatafeeding appendages. Limnol Oceanogr 40: 263–272
Harada K, Mayumi T, Shimada T, Suzuki M, Kondo F, Watanabe MF (1993) Occurrence of four depsipeptides, aeruginopeptins, together with microcystins from toxic cyanobacteria. Tetrahedron Lett. 34, 6091–6094
Harada KI, Kiyonaga F, Shimada T, Suzuki M, Sano H, Adachi K, Carmichael WW (1995) Two cyclic peptides, anabaenopeptins, a third group ofbioactive compounds from the cyanobacterium Anabaena flos-aquaeNRC 525-17. Tetrahedron Lett 36: 1511–1514
Helms GL, Moore RE, Niemczura WP, Patterson GML, Tomer KB, Gross ML (1988) Scytonemin A, a novel calcium antagonist from a blue-green alga. J Org Chem 53: 1298–1307
Honkanen RE, Codispoti BA, Tse K, Boynton AL (1994) Characterization of natural toxins with inhibitory activity against serine/threonine protein phosphatases. Toxicon 32: 339–350
Hughes EO, Gorham PR, Zahnder A (1958) Toxicity of an unialgal culture of Microcystis aeruginosa. Can J Microbiol 4: 225–236
Ishida K, Matsuda H, Murakami M, Yamaguchi K (1997) Micropeptins 478-A and -B, plasmin inhibitors from the cyanobacterium Microcystis aeruginosa. J Nat Prod 60:184– 187
Ishida K, Murakami M, Matsuda H, Yamaguchi K (1995) Micropeptin 90, a plasmin and trypsin inhibitor from the blue-green alga Microcystis aeruginosa(NIES-90). Tetrahedron Lett 36: 3535–3538
Ishitsuka MO, Kusumi T, Kakisawa H, Kaya K, Watanabe MM (1990) Microviridin: A novel tricyclic depsipeptide from the toxic cyanobacterium Microcystis viridis. J Am Chem Soc 112: 8180–8182
Jakobi C, Oberer L, Quiquerez C, Konig WA, Weckesser J (1995) Cyanopeptolin S, a sulfate-containing depsipeptide from a water bloom of Microcystissp.. FEMS Lett 129: 129–134
Jakobi C, Rinehart KL, Neuber R, Mez K, Weckesser J (1996) Cyanopeptolin SS, a disulfated depsipeptide from a water bloom in Leipzig (Germany): structural elucidation and biological activities. Phycologia 35: 111–116
Johnston NAL, Campagna VS, Hawkins PR, Banens RJ (1994) Response of the eastern rainbowfish (Melanotaenia duboulayi) to toxic Microcystis aeruginosa. Aust J Mar Freshwat Res 45: 917–923
Jungmann D (1992) Toxic compounds isolated from Microcystis PCC7806 that are more active against Daphniathan two microcystins. Limnol Oceanogr 37: 1777–1783
Kleinkauf H, von Dohren H (1996) A nonribosomal system of peptide biosynthesis. Eur J Biochem 236: 335–351
Kleinkauf H, von Dohren H. (1990) Nonribosomal biosynthesis of peptide antibiotics. Eur J Biochem 192: 1–15
Kobayashi J, Sato M, Ishibashi M, Shigemori H, Nakamura T, Ohizumi Y (1991a) Keramamide A, a novel peptide from the Okinawan marine sponge Theonellasp.. J Chem Soc Perkin Trans 1: 2609–2611
Kobayashi J, Sato M, Murayama T, Ishibashi M, Walchi MR, Kainai M, Shoji J, Ohizumi Y (1991b) Konbamide, a novel peptide with calmodium antagonistic activity from the Okinawan marine sponge Theonellasp.. J Chem Soc Chem Commun 15: 1050–1052
Kobayashi M, Kurosu N, Ohyabu N, Wang W, Kitagawa I (1994) The absolute stereostructure of arenastatin A, a potent cytotoxic depsipeptide from the Okinawan marine sponge Dysidea arenaria. Chem Pharm Bull 42: 2196–2198
Kodani S, Ishida K, Murakami M (1998) Aeruginosin 103-A, a thrombin inhibitor from the cyanobacterium Microcystis viridis. J Nat Prod 61: 1046–1048
Kusumi T, Ooi T, Watanabe MM, Takahashi H, Kakisawa H (1987) Cyanoviridin-RR, a toxin from the cyanobacterium Microcystis viridis. Tetrahedron Lett 28: 4695–4698
Lawton LA, Edwards C, Codd GA (1994) Extraction and high-performance liquid chromatographic method for the determination of microcystins in raw and treated waters. Analyst 119: 1525–1530
Lee AY, Smitka TA, Bonjouklian R, Clardy J (1994) Atomic structure of the trypsin-A90720A complex: a unified approach to structure and function. Chem Biol 1: 113–117
Lir&s V, Lindberg M, Nystrom P, Annadotter H, Lawton LA, Graf B (1998) Can ingested cyanobacteria be harmful to the signal crayfish (Pacifastacus leniusculus)? Freshwater Biol 39: 233 — 242
MacKintosh C, Beattie KA, Klumpp S, Cohen P, Codd GA (1990) Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2a from both mammals and higher plants. FEBS Lett 264: 187–192
Martin C, Oberer L, Ino T, Konig WA, Busch M, Weckesser J (1993) Cyanopeptolins, new depsipeptides from the cyanobacterium Microcystissp. PCC 7806. J Antibiot 46: 1550–1556
Martin C, Oberer L, Koenig WA, Busch M, Weckesser J (1990) Rapid purification of peptide toxins microcystin-LR and nodularin. FEMS Microbiol Lett 56: 1–5
Moon SS, Chen JL, Moore RE, Patterson GML (1992) Calophycin, a fungicidal cyclic decapeptide from the terrestrial blue-green alga Calothrix fusca. J Org Chem 57: 1097–1103
Moore RE (1996) Cyclic peptides and depsipeptides from cyanobacteria: a review. J Ind Microbiol 16: 134–143
Moore RE, Bornemann V, Niemczura WP, Gregson JM, Chen JL, Norton TR, Patterson GML, Herms GL (1989) Puwainaphycin C, a cardioactive cyclic peptide from the blue-green alga AnabaenaBQ-16–1. Use of two-dimensional 13C-13C and 13C-15N correlation spectroscopy in sequencing the amino acid units. J Am Chem Soc 111: 6128–6132
Moore RE, Corbett TH, Patterson GML, Valeriote FA (1996) The search for new antitumor drugs from blue-green algae. Curr Pharm Design 2: 317–330
Moore RE, Mynderse JS (1982) Majusculamide C. US Patent 4342751 Aug Murakami M, Okita Y, Matsuda H, Okino T, Yamaguchi K (1994) Aeruginosin 298-A, a thrombin and trypsin inhibitor from the blue-green alga Microcystis aeruginosa(NIES-298) Tetrahedron Lett 35: 3129–3132
Murakami M, Ishida K, Okino T, Okita Y, Matsuda H, Yamaguchi K (1995) Aeruginosas 98-A and -B, trypsin inhibitors from the blue-green alga Microcystis aeruginosa(NIES-98). Tetrahedron Lett 36: 2785–2788
Murakami M, Shin HJ, Matsuda H, Ishida K, Yamaguchi K (1997a) A cyclic peptide, Anabaenopeptin B, from the cyanobacterium Oscillatoria agardhii. Phytochemistry 44: 449–452
Murakami M, Kodani S, Ishida K, Matsuda H, Yamaguchi K (1997b) Micropeptin 103, a chymotrypsin inhibitor from the cyanobacterium Microcystis viridis(NIES-103). Tetrahedron Lett 38: 3035–3038
Namikoshi M, Choi BW, Sakai R, Sun F, Rinehart KL, Carmichael WW, Evans WR, Cruz P, Munro MHG, Blunt JW (1994) New nodularins, a general method for structure assignment. J Org Chem 59: 2349–2357
Namikoshi M, Rinehart KL (1996) Bioactive compounds produced by cyanobacteria. J Ind Microbiol 17: 373–384
Neumann U, Forchert A, Flury T, Weckesser J (1997) Microginin FR1, a linear peptide from a water bloom of Microcystisspecies. FEMS Microbiol Lett 153: 475–478
Oberemm A, Becker J, Codd G, Steinberg C (1999) Effects of cyanobacterial toxins and aqueous crude extracts on the development of fish and amphibians. Environ Toxicol 14: 77–88
Oberemm A, Fastner J, Steinberg CEW (1997) Effects of microcystin-LR and cyanobacterial crude extracts on embryo-larval development of zebrafish (Danio rerio). Wat Res 31: 2918–2921
Okino T, Matsuda H, Murakami M, Yamaguchi K (1993) Microginin, an angiotensin-converting enzyme inhibitor from the blue-green alga Microcystis aeruginosa. Tetrahedron Lett 34: 501–504
Okino T, Murakami M, Haraguchi R, Munekata H, Matsuda H, Yamaguchi K (1993b) Micropeptins A and B, plasmin and trypsin inhibitors from the blue-green algae Microcystis aeruginosa. Tetrahedron Lett 34: 8131–8134
Okino T, Matsuda H, Murakami M, Yamaguchi K (1995) New microviridins, elastase inhibitors from the blue-green alga Microcystis aeruginosa. Tetrahedron 51: 10679–10686
Papendorf 0, Koenig G M, Wright A D, Chorus I, Oberemm A (1997) Mueggelone, a novel inhibitor of fish development from the fresh water cyanobacterium Aphanizomenon flos aquae. J Nat Prod 60: 1298–1300
Patterson GML, Larsen LK, Moore RE (1994) Bioactive natural products from blue-green algae. J Appl Phycol 6: 151–157
Pergament I, Carmeli S (1994) Schizotrin A, a novel antimicrobial cyclic peptide from a cyanobacterium. Tetrahedron Lett 36: 8473–8476
Pettit GR, Kamano Y, Herald CL, Dufresne C, Cerny RL, Herald DL, Schmidt JM, Kizu H (1989) Isolation and structure of the cytostatic depsipeptide dolastatin 13 from the sea hare Dolabella auricularia. JAm Chem Soc 111: 5015–5017
Pettit GR, Kamano Y, Herald CL, Fujii Y, Kizu H, Boyd MR, Boettner FE, Doubek DL, Schmidt JL, Chapuis JC, Michel C (1993) Isolation of dolastatins 10–15 from the marine mollusc Dolabella auricularia. Tetrahedron 49: 9151–9170
Pilotto L, Douglas R, Burch M, Cameron S, Beers M, Rouch G, Robinson P, Kirk M, Cowie C, Hardiman S, Moore C, Attewell R (1997) Health effects of exposure to cyanobacteria (blue- green algae) during recreational water-related activities. Austral. New Zealand J Public Health 21: 562–566
Prepas EE, Kotak BG, Campbell JC, Evans JC, Hrudey SE, Holmes CFB (1997) Accumulation and elimination of cyanobacterial hepatotoxins by the freshwater clam Anodonta grandis simpsoniana. Can J Fish Aquat Sci 54: 41–46
Prinsep MR, Moore RE, Levine LA, Patterson GML (1992) Westiellamide, a bistratamide-related cyclic peptide from the blue-green algae Westiellopsis prolifica. J Natural Prod 55: 140–142
Reinikainen M, Kiviranta J, Ulvi V, Niku Paavola ML (1995) Acute toxic effects of a novel cyanobacterial toxin on the crustaceans Artemia salinaand Daphnia pulex. Arch Hydrobiol 133: 61–69
Richter K, Egger R, Kreil G (1987) D-alanine in the frog skin peptide dermorphin is derived from L-alanine in the precursor. Science 238: 200–202
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 Env Microbiol 65:737–739
Rompp Chemielexikon (1995) Vol. 2,9th edition, p. 891. Edited by J. Falbe, and M. Regitz. Thieme- Verlag, Stuttgart
Runnegar M, Berndt N, Kaplowitz N (1995) Microcystin uptake and inhibition of protein phosphatases: effects of chemoprotectants and self-inhibition in relation to known hepatic transporters. Toxicol Appl Pharmacol 134: 264–272
Sano T, Kaya K (1995) Oscillamide Y, a chymotrypsin inhibitor from toxic cyanobacteria.Tetrahedron Lett 36: 5933–5936
Shin HJ, Murakami M, Matsuda H, Ishida K, Yamaguchi K (1995) Oscillapeptin, an elastase and chymotrypsin inhibitor from the cyanobacterium Oscillatoria agardhii(NIES-204). Tetrahedron Lett 36: 5235–5238
Shin HJ, Matsuda H, Murakami M, Yamaguchi K (1997a) Anabaenopeptins E and F, two new cyclic peptides from the cyanobacterium Oscillatoria agardhii(NIES-204). J Nat Prod 60: 139–141
Shin HJ, Matsuda H, Murakami M, Yamaguchi K (1997b) Aeruginosas 205A and -B, serine protease inhibitory glycopeptides from the cyanobacterium Oscillatoria agardhii(NIES-205). J Org Chem 62: 1810–1813
Sivonen K, Jones J (1999) Cyanobacterial toxins. In: Chorus I, Bartram J (eds) Toxic cyanobacteria in water: a guide to their public health consequences, monitoring and management. Published on the behalf of WHO by E & FN Spon, London, pp. 41–111
Stratmann K, Burgoyne DL, Moore RE, Patterson GML, Smith CD (1994) Hapalosin, a cyanobacterial cyclic depsipeptide with multidrug-resistance reversing activity. J Org Chem 59: 7219–7226
Tencalla FG, Dietrich DR, Schlatter C (1994) Toxicity of Microcystis aeruginosapeptide toxin to yearling rainbow trout (Oncorhynchus mykiss). Aquat Toxicol 30: 215–224
Trimurtulu G, Ohtani I, Patterson GML, Moore RE, Corbett TH, Valeriote FA, Demchik L (1994) Total structures of cryptophycins, potent antitumor depsipeptides from the blue-green alga Nostocsp. strain GSV 224. J Am Chem Soc 116: 4729–4737
Tsukamoto S, Painuly P, Young KA, Yang X, Shimizu Y, Cornell 1 (1993) Microcystilide A: a novel cell-differentiation-promoting depsipeptide from Microcystis aeruginosaNO-15-1840. J Am Chem Soc 115: 11046 — 11047
Vasconcelos VM (1995) Uptake and depuration of the heptapeptide toxin microcystin-LR in Mytilus galloprovincialis. Aquat Toxicol 32: 227–237
Weckesser J, Martin C, Jakobi C (1996) Cyanopeptolins, depsipeptides from cyanobacteria. System Appl Microbiol 19: 133–138
Williams DE, Burgoyne DL, Retting SJ, Andersen RJ, Fahti-Afshar ZR, Allen TM (1993) The isolation of majusculamide C from the sponge Ptilocaulis trachyscollected in Enewetak and determination of the absolute configuration of the 2-methyl-3-aminopentanoic acid residue. J Nat Prod 56: 545–551
Williams DE, Craig M, Holmes CFB, Andersen RJ (1996) Ferintoic acid A and B, new cyclic hexapeptides from freshwater cyanobacterium Microcystis aeruginosa. J Nat Prod 59: 570–575
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Chorus, I. (2001). Toxic Effects and Substances in Cyanobacteria other than Microcystins, Anatoxin-a and Saxitoxins. In: Chorus, I. (eds) Cyanotoxins. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59514-1_7
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