Complement Modulating and Anticoagulant Effects of a Sulfated Exopolysaccharide Released by the Cyanobacterium Synechocystis aquatilis

Abstract

During batch cultivation, the cyanobacterial strain Synechocystis aquatilis Sauvageau B90.79 was found to release a fucose-rich sulfated polysaccharide, which was mainly composed of arabinose (45 %) and fucose (47 %) and had a degree of sulfation of 0.43. The released polysaccharide showed merely an anticoagulant activity of less than 10 % compared to the reference compound, unfractionated heparin. However, distinctive effects on the complement activation were observed: its inhibitory effect on the classical pathway of complement activation was 600-fold stronger than that of unfractionated heparin, whereas that on the alternative pathway of complement activation was 2- to 3-fold weaker. The results indicate that this biotechnologically producible, released polysaccharide represents a specifically acting complement modulator.

References

• 1 Singh S, Kate B N, Banerjee U C. Bioactive compounds from cyanobacteria and microalgae: an overview.  Crit Rev Biotechnol. 2005;  25 73-95
• 2 Schlösser U G. SAG-Sammlung von Algenkulturen at the University of Göttingen.  Bot Acta. 1994;  107 113-86
• 3 Drews G, Weckesser J. Function, structure and composition of cell walls and external layers. In: Carr NG, Whitton BA, editors Botanical Monographs; Vol. 19. The biology of cyanobacteria. Berkeley; University of California Press 1982: 333-58
• 4 De Philippis R, Faraloni C, Margheri M C, Sili C, Herdman M, Vincenzini M. Morphological and biochemical characterization of the exocellular investments of polysaccharide-producing Nostoc strains from the Pasteur Culture Collection.  World J Microbiol Biotechnol. 2000;  16 655-61
• 5 Berteau O, Mulloy B. Sulfated fucans, fresh perspectives: structures, functions, and biological properties of sulfated fucans and an overview of enzymes active towards this class of polysaccharide.  Glycobiology. 2003;  13 R29-40
• 6 Tissot B, Montdargent B, Chevolot L, Varenne A, Descroix S, Gareil P. et al . Interaction of fucoidan with the proteins of the complement classical pathway.  Biochim Biophys Acta. 2003;  1651 5-16
• 7 Tissot B, Daniel R. Letter to the Glyco-Forum: Biological properties of sulphated fucans: the potent inhibiting activity of algal fucoidan against the human complement system.  Glycobiology. 2003;  13 G29-30
• 8 Alban S, Classen B, Brunner G, Blaschek W. Differentiation between the complement modulating effects of an arabinogalactan-protein from Echinacea purpurea and heparin.  Planta Med. 2002;  68 1118-24
• 9 DePhilippis R, Vincenzini M. Exocellular polysaccharides from cyanobacteria and their possible applications.  FEMS Microbiol Rev. 1998;  22 151-75
• 10 Lee J -B, Hayashi T, Hayashi K, Sanakawa U, Maeda M, Nemoto T. et al . Further purification and structural analysis of calcium spirulan from Spirulina platensis .  J Nat Prod. 1998;  61 1101-4
• 11 Panoff J M, Priem B, Morvan H, Joset F. Sulfated exopolysaccharides produced by two unicellular strains of cyanobacteria, Synechocystis PCC 6803 and 6714.  Arch Mikrobiol. 1988;  150 558-63
• 12 Alban S. From heparins to factor Xa inhibitors and beyond.  Eur J Clin Invest. 2005;  35 Suppl 1 12-20
• 13 Alban S, Stibich H, Franz G. Pullulan sulfates and curdlan sulfates differ in their anticoagulant and anticomplementary action profile.  Phytomedicine. 2000;  7 Suppl II 47
• 14 Blondin C, Chaubet F, Nardella A, Sinquin C, Jozefonvicz J. Relationships between chemical characteristics and anticomplementary activity of fucans.  Biomaterials. 1996;  17 597-603
• 15 Pohl P, Kohlhase M, Krautwurst S, Baasch K H. An inexpensive inorganic culture medium for the mass cultivation of freshwater microalgae.  Phytochemistry. 1987;  26 1657-9
• 16 Volk R B. Screening of microalgal culture media for the presence of algicidal compounds and isolation and identification of two bioactive metabolites, excreted by the cyanobacteria Nostoc insulare and Nodularia harveyana, respectively.  J Appl Phycol. 2005;  17 339-47
• 17 Blakeney A B, Harris P J, Stone B A. A simple and rapid preparation of alditol acetates for monosaccharide analysis.  Carbohydr Res. 1983;  113 291-9
• 18 Blumenkrantz N, Asboe-Hansen G. New quantitative determination of uronic acids.  Anal Biochem. 1973;  54 484-9
• 19 Alban S, Franz G. Partial synthetic glucan sulfates as potential new antithrombotics: a review.  Biomacromolecules. 2001;  2 354-61
• 20 Classen B, Witthohn K, Blaschek W. Characterization of an arabinogalactan-protein isolated from pressed juice of Echinacea purpurea by precipitation with the β-glucosyl Yariv reagent.  Carbohydr Res. 2000;  327 97-504
• 21 Türk H, Haag R, Alban S. Dendritic polyglycerol sulfates as heparin analogues and potent inhibitors of the complement system.  Bioconjug Chem. 2004;  15 162-7