TY - JOUR A1 - Schuurmans, Jasper Merijn A1 - Brinkmann, Bregje W. A1 - Makower, Katharina A1 - Dittmann, Elke A1 - Huisman, Jef A1 - Matthijs, Hans C. P. T1 - Microcystin interferes with defense against high oxidative stress in harmful cyanobacteria JF - Harmful algae N2 - Harmful cyanobacteria producing toxic microcystins are a major concern in water quality management. In recent years, hydrogen peroxide (H2O2) has been successfully applied to suppress cyanobacterial blooms in lakes. Physiological studies, however, indicate that microcystin protects cyanobacteria against oxidative stress, suggesting that H2O2 addition might provide a selective advantage for microcystin-producing (toxic) strains. This study compares the response of a toxic Microcystis strain, its non-toxic mutant, and a naturally non-toxic Microcystis strain to H2O2 addition representative of lake treatments. All three strains initially ceased growth upon H2O2 addition. Contrary to expectation, the non-toxic strain and non-toxic mutant rapidly degraded the added H2O2 and subsequently recovered, whereas the toxic strain did not degrade H2O2 and did not recover. Experimental catalase addition enabled recovery of the toxic strain, demonstrating that rapid H2O2 degradation is indeed essential for cyanobacterial survival. Interestingly, prior to H2O2 addition, gene expression of a thioredoxin and peroxiredoxin was much lower in the toxic strain than in its non-toxic mutant. Thioredoxin and peroxiredoxin are both involved in H2O2 degradation, and microcystin may potentially suppress their activity. These results show that microcystin-producing strains are less prepared for high levels of oxidative stress, and are therefore hit harder by H2O2 addition than non-toxic strains. KW - Cyanobacteria KW - Harmful algal blooms KW - Microcystins KW - Hydrogen peroxide KW - Microarrays KW - Microcystis aeruginosa Y1 - 2018 U6 - https://doi.org/10.1016/j.hal.2018.07.008 SN - 1568-9883 SN - 1878-1470 VL - 78 SP - 47 EP - 55 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Hackenberg, Claudia A1 - Hakanpaeae, Johanna A1 - Cai, Fei A1 - Antonyuk, Svetlana A1 - Eigner, Caroline A1 - Meissner, Sven A1 - Laitaoja, Mikko A1 - Janis, Janne A1 - Kerfeld, Cheryl A. A1 - Dittmann, Elke A1 - Lamzin, Victor S. T1 - Structural and functional insights into the unique CBS-CP12 fusion protein family in cyanobacteria JF - Proceedings of the National Academy of Sciences of the United States of America N2 - 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. KW - crystal structure KW - hexamer KW - redox KW - Microcystis aeruginosa Y1 - 2018 U6 - https://doi.org/10.1073/pnas.1806668115 SN - 0027-8424 VL - 115 IS - 27 SP - 7141 EP - 7146 PB - National Acad. of Sciences CY - Washington ER - TY - JOUR A1 - Hu, Chenlin A1 - Ludsin, Stuart A. A1 - Martin, Jay F. A1 - Dittmann, Elke A1 - Lee, Jiyoung T1 - Mycosporine-like amino acids (MAAs)-producing Microcystis in Lake Erie BT - Development of a qPCR assay and insight into its ecology JF - Harmful algae N2 - Mycosporine-like amino acids (MAAs) are UV-absorbing metabolites found in cyanobacteria. While their protective role from UV in Microcystis has been studied in a laboratory setting, a full understanding of the ecology of MAA-producing versus non-MAA-producing Microcystis in natural environments is lacking. This study presents a new tool for quantifying MAA-producing Microcystis and applies it to obtain insight into the dynamics of MAA-producing and non-MAA-producing Microcystis in Lake Erie. This study first developed a sensitive, specific TaqMan real-time PCR assay that targets MAA synthetase gene C (mysC) of Microcystis (quantitative range: 1.7 × 101 to 1.7 × 107 copies/assay). Using this assay, Microcystis was quantified with a MAA-producing genotype (mysC+) in water samples (n = 96) collected during March-November 2013 from 21 Lake Erie sites (undetectable − 8.4 × 106 copies/ml). The mysC+ genotype comprised 0.3–37.8% of the Microcystis population in Lake Erie during the study period. The proportion of the mysC+ genotype during high solar UV irradiation periods (mean = 18.8%) was significantly higher than that during lower UV periods (mean = 9.7%). Among the MAAs, shinorine (major) and porphyra (minor) were detected with HPLC-PDA-MS/MS from the Microcystis isolates and water samples. However, no significant difference in the MAA concentrations existed between higher and lower solar UV periods when the MAA concentrations were normalized with Microcystis mysC abundance. Collectively, this study’s findings suggest that the MAA-producing Microcystis are present in Lake Erie, and they may be ecologically advantageous under high UV conditions, but not to the point that they exclusively predominate over the non-MAA-producers. KW - Shinorine KW - Porphyra KW - UV irradiation KW - Sunscreen KW - Eutrophication KW - Harmful algal bloom Y1 - 2018 U6 - https://doi.org/10.1016/j.hal.2018.05.010 SN - 1568-9883 SN - 1878-1470 VL - 77 SP - 1 EP - 10 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Dehm, Daniel A1 - Krumbholz, Julia A1 - Baunach, Martin A1 - Wiebach, Vincent A1 - Hinrichs, Katrin A1 - Guljamow, Arthur A1 - Tabuchi, Takeshi A1 - Jenke-Kodama, Holger A1 - Süssmuth, Roderich D. A1 - Dittmann-Thünemann, Elke T1 - Unlocking the spatial control of secondary metabolism uncovers hidden natural product diversity in nostoc punctiforme JF - ACS chemical biology N2 - Filamentous cyanobacteria belong to the most prolific producers of structurally unique and biologically active natural products, yet the majority of biosynthetic gene clusters predicted for these multicellular collectives are currently orphan. Here, we present a systems analysis of secondary metabolite gene expression in the model strain Nostoc punctiforme PCC73102 using RNA-seq and fluorescence reporter analysis. Our data demonstrate that the majority of the cryptic gene clusters are not silent but are expressed with regular or sporadic pattern. Cultivation of N. punctiforme using high-density fermentation overrules the spatial control and leads to a pronounced upregulation of more than 50% of biosynthetic gene clusters. Our data suggest that a combination of autocrine factors, a high CO2 level, and high light account for the upregulation of individual pathways. Our overarching study not only sheds light on the strategies of filamentous cyanobacteria to share the enormous metabolic burden connected with the production of specialized molecules but provides an avenue for the genome-based discovery of natural products in multicellular cyanobacteria as exemplified by the discovery of highly unusual variants of the tricyclic peptide microviridin. Y1 - 2019 U6 - https://doi.org/10.1021/acschembio.9b00240 SN - 1554-8929 SN - 1554-8937 VL - 14 IS - 6 SP - 1271 EP - 1279 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Barchewitz, Tino A1 - Guljamow, Arthur A1 - Meißner, Sven A1 - Timm, Stefan A1 - Henneberg, Manja A1 - Baumann, Otto A1 - Hagemann, Martin A1 - Dittmann, Elke T1 - Non-canonical localization of RubisCO under high-light conditions in the toxic cyanobacterium Microcystis aeruginosa PCC7806 JF - Environmental microbiology N2 - The frequent production of the hepatotoxin microcystin (MC) and its impact on the lifestyle of bloom-forming cyanobacteria are poorly understood. Here, we report that MC interferes with the assembly and the subcellular localization of RubisCO, in Microcystis aeruginosa PCC7806. Immunofluorescence, electron microscopic and cellular fractionation studies revealed a pronounced heterogeneity in the subcellular localization of RubisCO. At high cell density, RubisCO particles are largely separate from carboxysomes in M. aeruginosa and relocate to the cytoplasmic membrane under high-light conditions. We hypothesize that the binding of MC to RubisCO promotes its membrane association and enables an extreme versatility of the enzyme. Steady-state levels of the RubisCO CO2 fixation product 3-phosphoglycerate are significantly higher in the MC-producing wild type. We also detected noticeable amounts of the RubisCO oxygenase reaction product secreted into the medium that may support the mutual interaction of M. aeruginosa with its heterotrophic microbial community. Y1 - 2019 U6 - https://doi.org/10.1111/1462-2920.14837 SN - 1462-2912 SN - 1462-2920 VL - 21 IS - 12 SP - 4836 EP - 4851 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Pancrace, Claire A1 - Ishida, Keishi A1 - Briand, Enora A1 - Pichi, Douglas Gatte A1 - Weiz, Annika R. A1 - Guljarmow, Arthur A1 - Scalvenzi, Thibault A1 - Sassoon, Nathalie A1 - Hertweck, Christian A1 - Dittmann, Elke A1 - Gugger, Muriel T1 - Unique Biosynthetic Pathway in Bloom-Forming Cyanobacterial Genus Microcystis Jointly Assembles Cytotoxic Aeruginoguanidines and Microguanidines JF - ACS chemical biology N2 - The cyanobacterial genus Microcystis is known to produce an elaborate array of structurally unique and biologically active natural products, including hazardous cyanotoxins. Cytotoxic aeruginoguanidines represent a yet unexplored family of peptides featuring a trisubstituted benzene unit and farnesylated arginine derivatives. In this study, we aimed at assigning these compounds to a biosynthetic gene cluster by utilizing biosynthetic attributes deduced from public genomes of Microcystis and the sporadic distribution of the metabolite in axenic strains of the Pasteur Culture Collection of Cyanobacteria. By integrating genome mining with untargeted metabolomics using liquid chromatography with mass spectrometry, we linked aeruginoguanidine (AGD) to a nonribosomal peptide synthetase gene cluster and coassigned a significantly smaller product to this pathway, microguanidine (MGD), previously only reported from two Microcystis blooms. Further, a new intermediate class of compounds named microguanidine amides was uncovered, thereby further enlarging this compound family. The comparison of structurally divergent AGDs and MGDs reveals an outstanding versatility of this biosynthetic pathway and provides insights into the assembly of the two compound subfamilies. Strikingly, aeruginoguanidines and microguanidines were found to be as widespread as the hepatotoxic microcystins, but the occurrence of both toxin families appeared to be mutually exclusive. Y1 - 2018 U6 - https://doi.org/10.1021/acschembio.8b00918 SN - 1554-8929 SN - 1554-8937 VL - 14 IS - 1 SP - 67 EP - 75 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Meyer, Sabine A1 - Mainz, Andi A1 - Kehr, Jan-Christoph A1 - Suessmuth, Roderich A1 - Dittmann, Elke T1 - Prerequisites of Isopeptide Bond Formation in Microcystin Biosynthesis JF - ChemBioChem : a European journal of chemical biology N2 - The biosynthesis of the potent cyanobacterial hepatotoxin microcystin involves isopeptide bond formation through the carboxylic acid side chains of d-glutamate and -methyl d-aspartate. Analysis of the in vitro activation profiles of the two corresponding adenylation domains, McyE-A and McyB-A(2), either in a didomain or a tridomain context with the cognate thiolation domain and the upstream condensation domain revealed that substrate activation of both domains strictly depended on the presence of the condensation domains. We further identified two key amino acids in the binding pockets of both adenylation domains that could serve as a bioinformatic signature of isopeptide bond-forming modules incorporating d-glutamate or d-aspartate. Our findings further contribute to the understanding of the multifaceted role of condensation domains in nonribosomal peptide synthetase assembly lines. KW - amino acids KW - biosynthesis KW - cyanobacteria KW - nonribosomal peptide KW - substrate specificity Y1 - 2017 U6 - https://doi.org/10.1002/cbic.201700389 SN - 1439-4227 SN - 1439-7633 VL - 18 SP - 2376 EP - 2379 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Guljamow, Arthur A1 - Barchewitz, Tino A1 - Große, Rebecca A1 - Timm, Stefan A1 - Hagemann, Martin A1 - Dittmann, Elke T1 - Diel Variations of Extracellular Microcystin Influence the Subcellular Dynamics of RubisCO in Microcystis aeruginosa PCC 7806 JF - Microorganisms : open access journal N2 - The ubiquitous freshwater cyanobacterium Microcystis is remarkably successful, showing a high tolerance against fluctuations in environmental conditions. It frequently forms dense blooms which can accumulate significant amounts of the hepatotoxin microcystin, which plays an extracellular role as an infochemical but also acts intracellularly by interacting with proteins of the carbon metabolism, notably with the CO2 fixing enzyme RubisCO. Here we demonstrate a direct link between external microcystin and its intracellular targets. Monitoring liquid cultures of Microcystis in a diel experiment revealed fluctuations in the extracellular microcystin content that correlate with an increase in the binding of microcystin to intracellular proteins. Concomitantly, reversible relocation of RubisCO from the cytoplasm to the cell’s periphery was observed. These variations in RubisCO localization were especially pronounced with cultures grown at higher cell densities. We replicated these effects by adding microcystin externally to cultures grown under continuous light. Thus, we propose that microcystin may be part of a fast response to conditions of high light and low carbon that contribute to the metabolic flexibility and the success of Microcystis in the field. KW - cyanobacterial bloom KW - Microcystis KW - microcystin KW - RubisCO KW - extracellular signaling Y1 - 2021 U6 - https://doi.org/10.3390/microorganisms9061265 SN - 2076-2607 VL - 9 IS - 6 PB - MDPI CY - Basel ER - TY - GEN A1 - Guljamow, Arthur A1 - Barchewitz, Tino A1 - Große, Rebecca A1 - Timm, Stefan A1 - Hagemann, Martin A1 - Dittmann, Elke T1 - Diel Variations of Extracellular Microcystin Influence the Subcellular Dynamics of RubisCO in Microcystis aeruginosa PCC 7806 T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - The ubiquitous freshwater cyanobacterium Microcystis is remarkably successful, showing a high tolerance against fluctuations in environmental conditions. It frequently forms dense blooms which can accumulate significant amounts of the hepatotoxin microcystin, which plays an extracellular role as an infochemical but also acts intracellularly by interacting with proteins of the carbon metabolism, notably with the CO2 fixing enzyme RubisCO. Here we demonstrate a direct link between external microcystin and its intracellular targets. Monitoring liquid cultures of Microcystis in a diel experiment revealed fluctuations in the extracellular microcystin content that correlate with an increase in the binding of microcystin to intracellular proteins. Concomitantly, reversible relocation of RubisCO from the cytoplasm to the cell’s periphery was observed. These variations in RubisCO localization were especially pronounced with cultures grown at higher cell densities. We replicated these effects by adding microcystin externally to cultures grown under continuous light. Thus, we propose that microcystin may be part of a fast response to conditions of high light and low carbon that contribute to the metabolic flexibility and the success of Microcystis in the field. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1154 KW - cyanobacterial bloom KW - Microcystis KW - microcystin KW - RubisCO KW - extracellular signaling Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-521287 SN - 1866-8372 IS - 1154 ER - TY - JOUR A1 - Baunach, Martin A1 - Chowdhury, Somak A1 - Stallforth, Pierre A1 - Dittmann-Thünemann, Elke T1 - The landscape of recombination events that create nonribosomal peptide diversity JF - Molecular biology and evolution : MBE N2 - Nonribosomal peptides (NRP) are crucial molecular mediators in microbial ecology and provide indispensable drugs. Nevertheless, the evolution of the flexible biosynthetic machineries that correlates with the stunning structural diversity of NRPs is poorly understood. Here, we show that recombination is a key driver in the evolution of bacterial NRP synthetase (NRPS) genes across distant bacterial phyla, which has guided structural diversification in a plethora of NRP families by extensive mixing andmatching of biosynthesis genes. The systematic dissection of a large number of individual recombination events did not only unveil a striking plurality in the nature and origin of the exchange units but allowed the deduction of overarching principles that enable the efficient exchange of adenylation (A) domain substrates while keeping the functionality of the dynamic multienzyme complexes. In the majority of cases, recombination events have targeted variable portions of the A(core) domains, yet domain interfaces and the flexible A(sub) domain remained untapped. Our results strongly contradict the widespread assumption that adenylation and condensation (C) domains coevolve and significantly challenge the attributed role of C domains as stringent selectivity filter during NRP synthesis. Moreover, they teach valuable lessons on the choice of natural exchange units in the evolution of NRPS diversity, which may guide future engineering approaches. KW - evolution KW - recombination KW - structural diversity KW - natural products KW - nonribosomal peptide synthetases KW - microbial ecology Y1 - 2021 U6 - https://doi.org/10.1093/molbev/msab015 SN - 0737-4038 SN - 1537-1719 VL - 38 IS - 5 SP - 2116 EP - 2130 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Köker, Latife A1 - Akçaalan, Reyhan A1 - Dittmann, Elke A1 - Albay, Meriç T1 - Depth profiles of protein-bound microcystin in Küçükçekmece Lagoon JF - Toxicon : an international journal devoted to the exchange of knowledge on the poisons derived from the tissues of plants and animals ; official journal of the International Society on Toxinology N2 - Microcystis is the most commonly found toxic cyanobacterial genus around the world and has a negative impact on the ecosystem. As a predominant producer of the potent hepatotoxin microcystin (MC), the genus causes outbreaks in freshwaters worldwide. Standard analytical methods that are used for the detection of microcystin variants can only measure the free form of microcystin in cells. Since microcystin was found as free and proteinbound forms in the cells, a significant proportion of microcystin is underestimated with analytical methods. The aim of the study was to measure protein-bound microcystins and determine the environmental factors that affect the binding of microcystin to proteins. Samples were taken at depths of surface, 1 m, 5 m, 10 m, 15 m, and 18 m in Kucukcekmece Lagoon to analyze depth profiles of two different microcystin forms from June to September 2012 at regular monthly intervals. Our findings suggest that the most important parameter affecting proteinbound microcystin at surface water is high light. Due to favorable environmental conditions such as temperature, light, and physicochemical parameters, the higher microcystin contents, both free and protein-bound MCs, were found in summer periods. KW - Microcystis KW - Microcystin KW - Protein-bound microcystin KW - Mcy gene KW - Kucukcekmece Lagoon Y1 - 2021 U6 - https://doi.org/10.1016/j.toxicon.2021.05.005 SN - 0041-0101 SN - 1879-3150 VL - 198 SP - 156 EP - 163 PB - Elsevier CY - Oxford ER - TY - GEN A1 - des Aulnois, Maxime Georges A1 - Réveillon, Damien A1 - Robert, Elise A1 - Caruana, Amandine A1 - Briand, Enora A1 - Guljamow, Arthur A1 - Dittmann, Elke A1 - Amzil, Zouher A1 - Bormans, Myriam T1 - Salt shock responses of Microcystis revealed through physiological, transcript, and metabolomic analyses T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - The transfer of Microcystis aeruginosa from freshwater to estuaries has been described worldwide and salinity is reported as the main factor controlling the expansion of M. aeruginosa to coastal environments. Analyzing the expression levels of targeted genes and employing both targeted and non-targeted metabolomic approaches, this study investigated the effect of a sudden salt increase on the physiological and metabolic responses of two toxic M. aeruginosa strains separately isolated from fresh and brackish waters, respectively, PCC 7820 and 7806. Supported by differences in gene expressions and metabolic profiles, salt tolerance was found to be strain specific. An increase in salinity decreased the growth of M. aeruginosa with a lesser impact on the brackish strain. The production of intracellular microcystin variants in response to salt stress correlated well to the growth rate for both strains. Furthermore, the release of microcystins into the surrounding medium only occurred at the highest salinity treatment when cell lysis occurred. This study suggests that the physiological responses of M. aeruginosa involve the accumulation of common metabolites but that the intraspecific salt tolerance is based on the accumulation of specific metabolites. While one of these was determined to be sucrose, many others remain to be identified. Taken together, these results provide evidence that M. aeruginosa is relatively salt tolerant in the mesohaline zone and microcystin (MC) release only occurs when the capacity of the cells to deal with salt increase is exceeded. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1130 KW - Microcystis aeruginosa KW - microcystin KW - salt stress KW - metabolomic KW - transcript Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-472405 SN - 1866-8372 IS - 1130 ER - TY - BOOK A1 - Dittmann-Thünemann, Elke T1 - Toxische Cyanobakterien auf dem Vormarsch : Überlebenskünstler und Meister der Naturstoffsynthese : Antrittsvorlesung 2010-06-16 Y1 - 2010 UR - http://info.ub.uni-potsdam.de/multimedia/show_projekt.php?projekt_id=59 PB - Univ.-Bibl. CY - Potsdam ER - TY - JOUR A1 - Voss, Björn A1 - Bolhuis, Henk A1 - Fewer, David P. A1 - Kopf, Matthias A1 - Möke, Fred A1 - Haas, Fabian A1 - El-Shehawy, Rehab A1 - Hayes, Paul A1 - Bergman, Birgitta A1 - Sivonen, Kaarina A1 - Dittmann-Thünemann, Elke A1 - Scanlan, Dave J. A1 - Hagemann, Martin A1 - Stal, Lucas J. A1 - Hess, Wolfgang R. T1 - Insights into the physiology and ecology of the brackish-water-adapted cyanobacterium nodularia spumigena CCY9414 based on a genome-transcriptome analysis JF - PLoS one N2 - Nodularia spumigena is a filamentous diazotrophic cyanobacterium that dominates the annual late summer cyanobacterial blooms in the Baltic Sea. But N. spumigena also is common in brackish water bodies worldwide, suggesting special adaptation allowing it to thrive at moderate salinities. A draft genome analysis of N. spumigena sp. CCY9414 yielded a single scaffold of 5,462,271 nucleotides in length on which genes for 5,294 proteins were annotated. A subsequent strand-specific transcriptome analysis identified more than 6,000 putative transcriptional start sites (TSS). Orphan TSSs located in intergenic regions led us to predict 764 non-coding RNAs, among them 70 copies of a possible retrotransposon and several potential RNA regulators, some of which are also present in other N2-fixing cyanobacteria. Approximately 4% of the total coding capacity is devoted to the production of secondary metabolites, among them the potent hepatotoxin nodularin, the linear spumigin and the cyclic nodulapeptin. The transcriptional complexity associated with genes involved in nitrogen fixation and heterocyst differentiation is considerably smaller compared to other Nostocales. In contrast, sophisticated systems exist for the uptake and assimilation of iron and phosphorus compounds, for the synthesis of compatible solutes, and for the formation of gas vesicles, required for the active control of buoyancy. Hence, the annotation and interpretation of this sequence provides a vast array of clues into the genomic underpinnings of the physiology of this cyanobacterium and indicates in particular a competitive edge of N. spumigena in nutrient-limited brackish water ecosystems. Y1 - 2013 U6 - https://doi.org/10.1371/journal.pone.0060224 SN - 1932-6203 VL - 8 IS - 3 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Meissner, Sven A1 - Fastner, Jutta A1 - Dittmann-Thünemann, Elke T1 - Microcystin production revisited conjugate formation makes a major contribution JF - Environmental microbiology N2 - 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. Y1 - 2013 U6 - https://doi.org/10.1111/1462-2920.12072 SN - 1462-2912 VL - 15 IS - 6 SP - 1810 EP - 1820 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Ziemert, Nadine A1 - Ishida, Keishi A1 - Weiz, Annika A1 - Hertweck, Christian A1 - Dittmann-Thünemann, Elke T1 - Exploiting the natural diversity of microviridin gene clusters for discovery of novel tricyclic depsipeptides N2 - Microviridins are ribosomally synthesized tricyclic depsipeptides produced by different genera of cyanobacteria. The prevalence of the microviridin gene clusters and the natural diversity of microviridin precursor sequences are currently unknown. Screening of laboratory strains and field samples of the bloom-forming freshwater cyanobacterium Microcystis via PCR revealed global occurrence of the microviridin pathway and an unexpected natural variety. We could detect 15 new variants of the precursor gene mdnA encoding microviridin backbones that differ in up to 4 amino acid positions from known isoforms of the peptide. The survey not only provides insights into the versatility of the biosynthetic enzymes in a closely related group of cyanobacteria, but also facilitates the discovery and characterization of cryptic microviridin variants. This is demonstrated for microviridin L in Microcystis aeruginosa strain NIES843 and heterologously produced variants. Y1 - 2010 UR - http://aem.asm.org/ U6 - https://doi.org/10.1128/AEM.02858-09 SN - 0099-2240 ER - TY - JOUR A1 - Neilan, Brett A. A1 - Pearson, Leanne A. A1 - Münchhoff, Julia A1 - Moffitt, Michelle C. A1 - Dittmann-Thünemann, Elke T1 - Environmental conditions that influence toxin biosynthesis in cyanobacteria JF - Environmental microbiology N2 - Over the past 15 years, the genetic basis for production of many cyanobacterial bioactive compounds has been described. This knowledge has enabled investigations into the environmental factors that regulate the production of these toxins at the molecular level. Such molecular or systems level studies are also likely to reveal the physiological role of the toxin and contribute to effective water resource management. This review focuses on the environmental regulation of some of the most relevant cyanotoxins, namely the microcystins, nodularin, cylindrospermopsin, saxitoxins, anatoxins and jamaicamides. Y1 - 2013 U6 - https://doi.org/10.1111/j.1462-2920.2012.02729.x SN - 1462-2912 VL - 15 IS - 5 SP - 1239 EP - 1253 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Ferir, Geoffrey A1 - Vermeire, Kurt A1 - Huskens, Dana A1 - Balzarini, Jan A1 - Van Damme, Els J. M. A1 - Kehr, Jan-Christoph A1 - Dittmann-Thünemann, Elke A1 - Swanson, Michael D. A1 - Markovitz, David M. A1 - Schols, Dominique T1 - Synergistic in vitro anti-HIV type 1 activity of tenofovir with carbohydrate-binding agents (CBAs) JF - Antiviral research N2 - Tenofovir, a well-known and highly prescribed anti-HIV-1 drug for the treatment of HIV/AIDS infections, has recently also shown its effectiveness as a potential microbicide drug in the prevention of HIV transmission. Here, we evaluated the combination of tenofovir with various members of the class of carbohydrate-binding agents (CBAs) targeting the glycans on the viral envelope gp120 for their anti-HIV efficacy. The tenofovir/CBA combinations predominantly showed synergistic antiviral activity using the median effect principle. These findings illustrate that combination of tenofovir with CBAs may increase the antiviral potency of the individual drugs and reducing the risk on potential side-effects. KW - Tenofovir KW - Carbohydrate-binding agents KW - HIV KW - Synergy KW - Microbicide Y1 - 2011 U6 - https://doi.org/10.1016/j.antiviral.2011.03.188 SN - 0166-3542 VL - 90 IS - 3 SP - 200 EP - 204 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Meissner, Sven A1 - Steinhauser, Dirk A1 - Dittmann-Thünemann, Elke T1 - Metabolomic analysis indicates a pivotal role of the hepatotoxin microcystin in high light adaptation of Microcystis JF - Environmental microbiology N2 - 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. Y1 - 2015 U6 - https://doi.org/10.1111/1462-2920.12565 SN - 1462-2912 SN - 1462-2920 VL - 17 IS - 5 SP - 1497 EP - 1509 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Hu, Chenlin A1 - Völler, Ginka A1 - Sussmuth, Roderich A1 - Dittmann-Thünemann, Elke A1 - Kehr, Jan-Christoph T1 - Functional assessment of mycosporine-like amino acids in Microcystis aeruginosa strain PCC 7806 JF - Environmental microbiology N2 - The biological role of the widespread mycosporine-like amino acids (MAAs) in cyanobacteria is under debate. Here, we have constructed and characterized two mutants impaired in MAA biosynthesis in the bloom-forming cyanobacterium Microcystis aeruginosaPCC 7806. We could identify shinorine as the sole MAA type of the strain, which is exclusively located in the extracellular matrix. Bioinformatic studies as wells as polymerase chain reaction screening revealed that the ability to produce MAAs is sporadically distributed within the genus. Growth experiments and reactive oxygen species quantification with wild-type and mutant strains did not support a role of shinorine in protection against UV or other stress conditions in M.aeruginosaPCC 7806. The shinorine content per dry weight of cells as well as transcription of the mys gene cluster was not significantly elevated in response to UV-A, UV-B or any other stress condition tested. Remarkably, both mutants exhibited pronounced morphological changes compared with the wild type. We observed an increased accumulation and an enhanced hydrophobicity of the extracellular matrix. Our study suggests that MAAs in Microcystis play a negligible role in protection against UV radiation but might be a strain-specific trait involved in extracellular matrix formation and cell-cell interaction. Y1 - 2015 U6 - https://doi.org/10.1111/1462-2920.12577 SN - 1462-2912 SN - 1462-2920 VL - 17 IS - 5 SP - 1548 EP - 1559 PB - Wiley-Blackwell CY - Hoboken ER -