The cyanobacterial hepatotoxin microcystin binds to proteins and increases the fitness of microcystis under oxidative stress conditions

• Published in: PloS one Vol. 6; no. 3; p. e17615
• Main Authors: Zilliges, Yvonne, Kehr, Jan-Christoph, Meissner, Sven, Ishida, Keishi, Mikkat, Stefan, Hagemann, Martin, Kaplan, Aaron, Börner, Thomas, Dittmann, Elke
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.03.2011; Public Library of Science (PLoS)
• Subjects: Abiotic stress; Anabaena; Binding; Biochemistry; Biology; Biosynthesis; Calvin cycle; Cell division; Cyanobacteria; Cysteine; Cystine; Daphnia; Data processing; Deficient mutant; Drinking water; Environmental conditions; Enzymes; Experiments; Fitness; Genes; Hepatotoxicity; Hydrogen; Hydrogen peroxide; Lakes; Light; Light effects; Metabolites; Microcystins; Microcystins - metabolism; Microcystis; Microcystis - enzymology; Microcystis - metabolism; Microcystis aeruginosa; Microorganisms; Mutagenesis; NADP; Oxidation-Reduction; Oxidative Stress; Peptides; Peroxides; Phycobiliproteins; Planktothrix agardhii; Plant metabolites; Proteases; Protein Binding; Proteinase; Proteins; reductase; Reductases; Ribulose-bisphosphate carboxylase; Ribulose-Bisphosphate Carboxylase - metabolism; Secondary metabolites; Stress response; Studies; Synechocystis; Toxins; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0017615

Microcystins are cyanobacterial toxins that represent a serious threat to drinking water and recreational lakes worldwide. Here, we show that microcystin fulfils an important function within cells of its natural producer Microcystis. The microcystin deficient mutant ΔmcyB showed significant changes in the accumulation of proteins, including several enzymes of the Calvin cycle, phycobiliproteins and two NADPH-dependent reductases. We have discovered that microcystin binds to a number of these proteins in vivo and that the binding is strongly enhanced under high light and oxidative stress conditions. The nature of this binding was studied using extracts of a microcystin-deficient mutant in vitro. The data obtained provided clear evidence for a covalent interaction of the toxin with cysteine residues of proteins. A detailed investigation of one of the binding partners, the large subunit of RubisCO showed a lower susceptibility to proteases in the presence of microcystin in the wild type. Finally, the mutant defective in microcystin production exhibited a clearly increased sensitivity under high light conditions and after hydrogen peroxide treatment. Taken together, our data suggest a protein-modulating role for microcystin within the producing cell, which represents a new addition to the catalogue of functions that have been discussed for microbial secondary metabolites.