Skip to main content
SpringerLink
Log in

Antifouling Bastadin Congeners Target Mussel Phenoloxidase and Complex Copper(II) Ions

  • Original Article
  • Published:
Marine Biotechnology Aims and scope Submit manuscript

Abstract

Synthetically prepared congeners of sponge-derived bastadin derivatives such as 5,5′-dibromohemibastadin-1 (DBHB) that suppress the settling of barnacle larvae were identified in this study as strong inhibitors of blue mussel phenoloxidase that is involved in the firm attachment of mussels to a given substrate. The IC50 value of DBHB as the most active enzyme inhibitor encountered in this study amounts to 0.84 μM. Inhibition of phenoloxidase by DBHB is likely due to complexation of copper(II) ions from the catalytic centre of the enzyme by the α-oxo-oxime moiety of the compound as shown here for the first time by structure activity studies and by X-ray structure determination of a copper(II) complex of DBHB.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aladaileh S, Rodney P, Nair SV, Raftos DA (2007) Characterization of phenoloxidase activity in Sydney rock oysters (Saccostrea glomerata). Comp Biochem Physiol B 148:470–480

    Article  PubMed  Google Scholar 

  • Asokan R, Arumugam M, Mullainadhan P (1997) Activation of prophenoloxidase in the plasma and haemocytes of the marine mussel Perna viridis Linnaeus. Dev Comp Immunol 21:1–12

    Article  PubMed  CAS  Google Scholar 

  • Blunt JW, Copp BR, Hu W-PH, Munro MHG, Northcote PT, Prinsep MR (2009) Marine natural products. Nat Prod Rep 26:170–244

    Article  PubMed  CAS  Google Scholar 

  • Chen JS, Wei C, Rolle RS, Otwell WS, Balaban MO, Marshall MR (1991) Inhibitory effect of kojic acid on some plant and crustacean polyphenol oxidases. J Agric Food Chem 39:1396–1401

    Article  CAS  Google Scholar 

  • Cheung PJ, Ruggieri GD, Nigrelli RF (1977) A new method for obtaining barnacle cement in the liquid state for polymerization studies. Mar Biol 43:157–163

    Article  Google Scholar 

  • Cima F, Ballarin L (2000) Tributyltin induces cytoskeletal alterations in the colonial ascidian Botryllus schlosseri phagocytes via interaction with calmodulin. Aquat Toxicol 48:419–429

    Article  PubMed  CAS  Google Scholar 

  • Cima F, Ballarin L, Bressa G, Burighel P (1998a) Cytoskeleton alterations of tributyltin (TBT), in lunicante phagocytes. Ecotoxicol Environ Saf 40:160–165

    Article  PubMed  CAS  Google Scholar 

  • Cima F, Spinazzi R, Ballarin L (1998b) Possible tributyltin–calmodulin interaction in morphofunctional alterationsof ascidian phagocytes. Fresenius Environ Bull 7:396–401

    Google Scholar 

  • Clare AS (1996) Signal transduction in barnacle settlement: calcium revisitied. Biofouling 10:141–159

    Article  CAS  Google Scholar 

  • Decker H, Schweikardt T, Tuczek F (2006) The first crystal structure of tyrosinase: all questions answered? Angew Chem 45:4546–4550

    Article  CAS  Google Scholar 

  • Fusetani N (2004) Biofouling and antifouling. Nat Prod Rep 21:94–104

    Article  PubMed  CAS  Google Scholar 

  • Hellio C, Yebra DM (2009) Legislation affecting antifouling products. In: Hellio C, Yebra DM (eds) Advances in marine antifouling coatings and technologies. Woodshead, Cambridge, pp 240–260

    Chapter  Google Scholar 

  • Hellio C, Bourgougnon N, Le Gal Y (2000) Phenoloxidase (E.C. 1.14.18.1) from Mytilus edulis byssus gland: purification, partial characterization and application for screening products with potential antifouling activities. Biofouling 16:235–244

    Article  CAS  Google Scholar 

  • Hellio C, Bado-Nilles A, Gagnaire B, Renault T, Thomas-Guyon H (2007) Demonstration of a true phenoloxidase activity and activation of a ProPO cascade in Pacific oyster, Crassostrea gigas (Thunberg) in vitro. Fish Shellfish Immunol 22:433–440

    Article  PubMed  CAS  Google Scholar 

  • Hellio C, Maréchal JP, Da Gama BAP, Pereira R, Clare AS (2009) Natural marine products with antifouling activities. In: Hellio C, Yebra D (eds) Advances in marine antifouling coatings and technologies. Woodshead, Cambridge, pp 572–622

    Chapter  Google Scholar 

  • IMO (2001). Resolution on early and effective application of the international convention on the control of harmful antifouling systems on ships. Resolution A928(22) IMO

  • Kamino K (2001) Novel barnacle underwater adhesive protein is a charged amino acid-rich protein constituted by a Cys-rich repetitive sequence. Biochem J 356:503–507

    Article  PubMed  CAS  Google Scholar 

  • Kapoor P, Pathak A, Kapoor R, Venugopalan P, Corbella M, Rodríguez M, Robles J, Llobet A (2002) Structural, electronic, and magnetic consequences of O-carbonyl vs O-alkoxy ester coordination in new dicopper complexes containing the Cu2(μ-Cl)2 core. Inorg Chem 41:6153–6160

    Article  PubMed  CAS  Google Scholar 

  • Kapoor P, Pathak A, Prabhjot K, Venugopalan P, Kapoor R (2004) Steric control of coordination: unusual coordination mode of dimethylpyridine-2,6-dicarboxylate in a new dinuclear copper(II) complex [(dmpc)(Cl)(μ-Cl)Cu2(μ-Cl)(Cl)(dmpc)] and reversal of the coordination mode in [Cu(dmpc) (H2O)3] (ClO4)2. Trans Met Chem 29:251–258

    Article  CAS  Google Scholar 

  • Kim YJ, Uyama H (2005) Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future. Cell Mol Life Sci 62:1707–1723

    Article  PubMed  CAS  Google Scholar 

  • Kim D, Park J, Kim J, Han C, Yoon J, Kim N, Seo J, Lee C (2006) Flavonoids as mushroom tyrosinase inhibitors: a fluorescence quenching study. J Agric Food Chem 54:935–941

    Article  PubMed  CAS  Google Scholar 

  • Kubo I, Kinst-Hori I, Chaudhuri SW, Kubo Y, Sánchez Y, Ogura T (2000) Flavonols from Heterotheca inuloides: tyrosinase inhibitory activity and structural criteria. Bioorg Med Chem 8:1749–1755

    Article  PubMed  CAS  Google Scholar 

  • Lau M (1991) Tributyltin antifouling: a treat to the Hong Kong marine environment. Arch Environ Contam Toxicol 20:299–304

    Article  PubMed  CAS  Google Scholar 

  • Liu D, Maguire R, Lau Y, Pacepavicius G, Okamura H, Aoyama I (1997) Transformation of the new antifouling compound Iragarol 1051 by Phanerochaete chrysosporium. Water Res 31:2363–2369

    Article  CAS  Google Scholar 

  • Maréchal JP, Hellio C (2009) Challenges for the development of new non-toxic antifouling solutions. Int J Mol Sci 10:4623–4637

    Article  PubMed  Google Scholar 

  • Mokrini R, Mesaoud MB, Daoudi M, Hellio C, Maréchal JP, El Hattab M, Ortalo-Magné A, Piovetti L, Culioli G (2008) Meroditerpenoids and derivatives from the brown alga Cystoseira baccata and their antifouling propoerties. J Nat Prod 71:1806–1811

    Article  PubMed  CAS  Google Scholar 

  • Nagasawa T, Utagawa T, Goto J, Kim CJ, Tani Y, Kumagai H, Yamada H (1981) Synthesis of L-tyrosine-related amino acids by tyrosine phenol-lyase of Citrobacter intermedius. Eur J Biochem 117:33–40

    Article  PubMed  CAS  Google Scholar 

  • Olivares C, García-Borrón J, Solano F (2002) Identification of active site residues involved in metal cofactor binding and stereospecific substrate recognition in mammalian tyrosinase. Implications catalytic cycle. Biochem 41:679–686

    Article  CAS  Google Scholar 

  • Ortlepp S, Sjögren M, Dahlström M, Weber H, Ebel R, Edrada RA, Thoms C, Schupp P, Bohlin L, Proksch P (2007) Antifouling activity of bromotyrosine-derived sponge metabolites and synthetic analogues. Mar Biotechnol 9:776–785

    Article  PubMed  CAS  Google Scholar 

  • Pereira M, Ankjaergaard C (2009) Legislation affecting antifouling products. In: Yebra D, Hellio C (eds) Advances in marine antifouling coatings and technologies. Woodshead, Cambridge, pp 240–260

    Chapter  Google Scholar 

  • Rittschof D, Maki J, Mitchell R, Costlow JD (1986) Ion and neuropharmacological studies of barnacle settlement. Neth J Sea Res 20:269–275

    Article  CAS  Google Scholar 

  • Sheldrick GM (1990) SHELXS97. Program for the solution of crystal structures. University of Göttingen, Germany

    Google Scholar 

  • Sheldrick GM (1997) SHELXL97. Program for the refinement of crystal structures. University of Göttingen, Germany

    Google Scholar 

  • Sommerer SO, Westcott BL, Jircitano AJ, Abboud KA (1995) The synthesis and structure of two novel metal-di-2-pyridyl ketone oxime dimers. Inorg Chim Acta 238:149–153

    Article  CAS  Google Scholar 

  • Suci PA, Geesey GG (2000) Influence of sodium periodate and tyrosinase on binding of alginate and adlayers of Mytilus edulis foot protein 1. J Colloid Interface Sci 230:340–348

    Article  PubMed  CAS  Google Scholar 

  • Tsoukatou M, Hellio C, Vagias C, Harvala C, Roussis V (2002) Chemical defense and antifouling activity of three Mediterranean sponges of the genus Ircinia. Z Naturforsch 57:161–171

    CAS  Google Scholar 

  • Tsoukatou M, Maréchal JP, Hellio C, Novaković I, Tufegdzic S, Sladić D, Gašić MJ, Clare AS, Vagias C, Roussis V (2007) Evaluation of the activity of the sponge metabolites avarol and avarone and their synthetic derivatives against fouling micro- and macroorganisms. Molecules 12:1022–1034

    Article  PubMed  CAS  Google Scholar 

  • Tujula N, Radford J, Nair SV, Raftor DA (2001) Effects of tributyltin and other metals on the phenoloxidase activation system of the tunicate, Styela plicata. Aquat Toxicol 55:191–201

    Article  PubMed  CAS  Google Scholar 

  • Voulvoulis N, Scrimshaw M, Lester J (1999) Alternative antifouling biocides. Appl Organometal Chem 13:135–145

    Article  CAS  Google Scholar 

  • Wahl N (1989) Marine epibiosis. 1 Fouling and antifouling—some basic aspects. Mar Ecol Prog Ser 58:175–189

    Article  Google Scholar 

  • Yamamoto H, Satuito CG, Yamazaki M, Natoyama K, Tachibana A, Fusetani N (1998) Neurotransmitter blockers as antifoulants against planktonic larvae of the barnacle Balanus amphitrite and the mussel Mytilus galloprovincialis. Biofouling 13:69–82

    Article  CAS  Google Scholar 

  • Yebra DM, Kiil S, Dam-Johansen K (2004) Antifouling technology: past, present and future steps towards efficient and environmentally friendly antifouling coatings. Progr Org Coating 50:75–104

    Article  CAS  Google Scholar 

  • Zentz F, Hellio C, Valla A, De La Broise D, Bremer G, Labia R (2002) Antifouling activities of N-substituated imides: antimicrobial activities and inhibition of Mytilus edulis phenoloxidase. Mar Biotechnol 4:431–430

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

The financial support of the BMBF to Peter Proksch under the project BiotecMarin is gratefully acknowledged. We thank the Industrieclub Düsseldorf e.V. for the financial support of Mirko Bayer and MOST for the support granted to Wenhan Lin. We, furthermore, thank Mrs. Eleonore Hammes for the technical assistance during the X-ray diffraction experiments.

Author information

Author notes

  1. Mirko Bayer

    Present address: Caesar & Loretz GmbH, Herderstr. 31, 40721, Hilden, Germany

Authors and Affiliations

  1. Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225, Düsseldorf, Germany

    Mirko Bayer & Peter Proksch

  2. Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225, Düsseldorf, Germany

    Horst Weber

  3. School of Biological Sciences, King Henry Building, Portsmouth University, Portsmouth, PO1 2DY, UK

    Claire Hellio & Jean-Philippe Maréchal

  4. Institut für Anorganische Chemie und Strukturchemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225, Düsseldorf, Germany

    Walter Frank

  5. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, No. 38 Xue Yuan Road, 100083, Beijing, People’s Republic of China

    Wenhan Lin

Authors
  1. Mirko Bayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claire Hellio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jean-Philippe Maréchal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Walter Frank
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenhan Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Horst Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter Proksch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Proksch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bayer, M., Hellio, C., Maréchal, JP. et al. Antifouling Bastadin Congeners Target Mussel Phenoloxidase and Complex Copper(II) Ions. Mar Biotechnol 13, 1148–1158 (2011). https://doi.org/10.1007/s10126-011-9378-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10126-011-9378-3

Keywords

Search

Navigation