@article{ZilligesKehrMeissneretal.2011, author = {Zilliges, Yvonne and Kehr, Jan-Christoph and Meissner, Sven and Ishida, Keishi and Mikkat, Stefan and Hagemann, Martin and Kaplan, Aaron and B{\"o}rner, Thomas and Dittmann-Th{\"u}nemann, Elke}, title = {The cyanobacterial hepatotoxin microcystin binds to proteins and increases the fitness of microcystis under oxidative stress conditions}, series = {PLoS one}, volume = {6}, journal = {PLoS one}, number = {3}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0017615}, pages = {11}, year = {2011}, abstract = {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 Delta mcyB 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.}, language = {en} } @article{HackenbergHakanpaeaeCaietal.2018, author = {Hackenberg, Claudia and Hakanpaeae, Johanna and Cai, Fei and Antonyuk, Svetlana and Eigner, Caroline and Meissner, Sven and Laitaoja, Mikko and Janis, Janne and Kerfeld, Cheryl A. and Dittmann, Elke and Lamzin, Victor S.}, title = {Structural and functional insights into the unique CBS-CP12 fusion protein family in cyanobacteria}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {27}, publisher = {National Acad. of Sciences}, address = {Washington}, issn = {0027-8424}, doi = {10.1073/pnas.1806668115}, pages = {7141 -- 7146}, year = {2018}, abstract = {Cyanobacteria are important photosynthetic organisms inhabiting a range of dynamic environments. This phylum is distinctive among photosynthetic organisms in containing genes encoding uncharacterized cystathionine beta-synthase (CBS)-chloroplast protein (CP12) fusion proteins. These consist of two domains, each recognized as stand-alone photosynthetic regulators with different functions described in cyanobacteria (CP12) and plants (CP12 and CBSX). Here we show that CBS-CP12 fusion proteins are encoded in distinct gene neighborhoods, several unrelated to photosynthesis. Most frequently, CBS-CP12 genes are in a gene cluster with thioredoxin A (TrxA), which is prevalent in bloom-forming, marine symbiotic, and benthic mat cyanobacteria. Focusing on a CBS-CP12 from Microcystis aeruginosa PCC 7806 encoded in a gene cluster with TrxA, we reveal that the domain fusion led to the formation of a hexameric protein. We show that the CP12 domain is essential for hexamerization and contains an ordered, previously structurally uncharacterized N-terminal region. We provide evidence that CBS-CP12, while combining properties of both regulatory domains, behaves different from CP12 and plant CBSX. It does not form a ternary complex with phosphoribulokinase (PRK) and glyceraldehyde-3-phosphate dehydrogenase. Instead, CBS-CP12 decreases the activity of PRK in an AMP-dependent manner. We propose that the novel domain architecture and oligomeric state of CBS-CP12 expand its regulatory function beyond those of CP12 in cyanobacteria.}, language = {en} } @article{MeissnerFastnerDittmannThuenemann2013, author = {Meissner, Sven and Fastner, Jutta and Dittmann-Th{\"u}nemann, Elke}, title = {Microcystin production revisited conjugate formation makes a major contribution}, series = {Environmental microbiology}, volume = {15}, journal = {Environmental microbiology}, number = {6}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1462-2912}, doi = {10.1111/1462-2920.12072}, pages = {1810 -- 1820}, year = {2013}, abstract = {The impact of environmental stimuli on the production of the widespread cyanobacterial hepatotoxin microcystin (MC) is under debate. Whereas transcriptional studies of the biosynthetic genes suggest a clear influence of light conditions on toxin production the data for the metabolite itself are inconsistent and highly strain-specific. Here, we have reassessed the MC content by using two immunological detection techniques that allow a parallel quantification of MC in the methanolic extracts and the residual pellet fraction that contains high molecular weight proteins. Our results show a significant proportion of MC in the protein bound fraction in strains of Microcystis and Planktothrix and of the related toxin nodularin (NOD) in Nodularia. Moreover, we could show a very strong increase of MC after high light illumination in the protein fraction contributing to a significant overall increase in MC production under these conditions that is not seen in extracts analysed by LC-MS and ELISA. The fact that a considerable portion of MC is neglected with current analysis techniques was also confirmed for selected field samples. Immunofluorescence studies suggest strain-specific differences in the amount of MC conjugate formation.}, language = {en} } @article{MeissnerSteinhauserDittmannThuenemann2015, author = {Meissner, Sven and Steinhauser, Dirk and Dittmann-Th{\"u}nemann, Elke}, title = {Metabolomic analysis indicates a pivotal role of the hepatotoxin microcystin in high light adaptation of Microcystis}, series = {Environmental microbiology}, volume = {17}, journal = {Environmental microbiology}, number = {5}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1462-2912}, doi = {10.1111/1462-2920.12565}, pages = {1497 -- 1509}, year = {2015}, abstract = {Microcystis is a freshwater cyanobacterium frequently forming nuisance blooms in the summer months. The genus belongs to the predominant producers of the potent hepatotoxin microcystin. The success of Microcystis and its remarkable resistance to high light conditions are not well understood. Here, we have compared the metabolic response of Microcystis aeruginosaPCC7806, its microcystin-deficient mcyB mutant (Mut) and the cyanobacterial model organism SynechocystisPCC6803 to high light exposure of 250molphotonsm(-2)s(-1) using GC/MS-based metabolomics. Microcystis wild type and Mut show pronounced differences in their metabolic reprogramming upon high light. Seventeen percent of the detected metabolites showed significant differences between the two genotypes after high light exposure. Whereas the microcystin-producing wild type shows a faster accumulation of glycolate upon high light illumination, loss of microcystin leads to an accumulation of general stress markers such as trehalose and sucrose. The study further uncovers differences in the high light adaptation of the bloom-forming cyanobacterium Microcystis and the model cyanobacterium Synechocystis. Most notably, Microcystis invests more into carbon reserves such as glycogen after high light exposure. Our data shed new light on the lifestyle of bloom-forming cyanobacteria, the role of the widespread toxin microcystin and the metabolic diversity of cyanobacteria.}, language = {en} }