@article{LiaimerJensenDittmann2016,
  author    = {Liaimer, Anton and Jensen, John B. and Dittmann, Elke},
  title     = {A Genetic and Chemical Perspective on Symbiotic Recruitment of Cyanobacteria of the Genus Nostoc into the Host Plant Blasia pusilla L.},
  series = {Frontiers in microbiology},
  volume    = {7},
  journal   = {Frontiers in microbiology},
  publisher = {Frontiers Research Foundation},
  address   = {Lausanne},
  issn      = {1664-302X},
  doi       = {10.3389/fmicb.2016.01693},
  pages     = {449 -- 474},
  year      = {2016},
  abstract  = {Liverwort Blasia pusilla L. recruits soil nitrogen-fixing cyanobacteria of genus Nostoc as symbiotic partners. In this work we compared Nostoc community composition inside the plants and in the soil around them from two distant locations in Northern Norway. STRR fingerprinting and 16S rDNA phylogeny reconstruction showed a remarkable local diversity among isolates assigned to several Nostoc clades. An extensive web of negative allelopathic interactions was recorded at an agricultural site, but not at the undisturbed natural site. The cell extracts of the cyanobacteria did not show antimicrobial activities, but four isolates were shown to be cytotoxic to human cells. The secondary metabolite profiles of the isolates were mapped by MALDI-TOF MS, and the most prominent ions were further analyzed by Q-TOF for MS/MS aided identification. Symbiotic isolates produced a great variety of small peptide-like substances, most of which lack any record in the databases. Among identified compounds we found microcystin and nodularin variants toxic to eukaryotic cells. Microcystin producing chemotypes were dominating as symbiotic recruits but not in the free-living community. In addition, we were able to identify several novel aeruginosins and banyaside-like compounds, as well as nostocyclopeptides and nosperin.},
  language  = {en}
}
@article{KrumbholzIshidaBaunachetal.2022,
  author    = {Krumbholz, Julia and Ishida, Keishi and Baunach, Martin and Teikari, Jonna and Rose, Magdalena M. and Sasso, Severin and Hertweck, Christian and Dittmann, Elke},
  title     = {Deciphering chemical mediators regulating specialized metabolism in a symbiotic cyanobacterium},
  series = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker. International edition},
  journal   = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker. International edition},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1433-7851},
  doi       = {10.1002/anie.202204545},
  pages     = {10},
  year      = {2022},
  abstract  = {Genomes of cyanobacteria feature a variety of cryptic biosynthetic pathways for complex natural products, but the peculiarities limiting the discovery and exploitation of the metabolic dark matter are not well understood. Here we describe the discovery of two cell density-dependent chemical mediators, nostoclide and nostovalerolactone, in the symbiotic model strain Nostoc punctiforme, and demonstrate their pronounced impact on the regulation of specialized metabolism. Through transcriptional, bioinformatic and labeling studies we assigned two adjacent biosynthetic gene clusters to the biosynthesis of the two polyketide mediators. Our findings provide insight into the orchestration of specialized metabolite production and give lessons for the genomic mining and high-titer production of cyanobacterial bioactive compounds.},
  language  = {en}
}
@article{KoekerAkcaalanDittmannetal.2021,
  author    = {K{\"o}ker, Latife and Ak{\c{c}}aalan, Reyhan and Dittmann, Elke and Albay, Meri{\c{c}}},
  title     = {Depth profiles of protein-bound microcystin in K{\"u}{\c{c}}{\"u}k{\c{c}}ekmece Lagoon},
  series = {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},
  volume    = {198},
  journal   = {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},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0041-0101},
  doi       = {10.1016/j.toxicon.2021.05.005},
  pages     = {156 -- 163},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@article{GuljamowBarchewitzGrosseetal.2021,
  author    = {Guljamow, Arthur and Barchewitz, Tino and Große, Rebecca and Timm, Stefan and Hagemann, Martin and Dittmann, Elke},
  title     = {Diel Variations of Extracellular Microcystin Influence the Subcellular Dynamics of RubisCO in Microcystis aeruginosa PCC 7806},
  series = {Microorganisms : open access journal},
  volume    = {9},
  journal   = {Microorganisms : open access journal},
  number    = {6},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2076-2607},
  doi       = {10.3390/microorganisms9061265},
  pages     = {14},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@misc{GuljamowBarchewitzGrosseetal.2021,
  author    = {Guljamow, Arthur and Barchewitz, Tino and Große, Rebecca and Timm, Stefan and Hagemann, Martin and Dittmann, Elke},
  title     = {Diel Variations of Extracellular Microcystin Influence the Subcellular Dynamics of RubisCO in Microcystis aeruginosa PCC 7806},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1154},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-52128},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-521287},
  pages     = {16},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@article{NwosuRoeserYangetal.2021,
  author    = {Nwosu, Ebuka Canisius and Roeser, Patricia Angelika and Yang, Sizhong and Ganzert, Lars and Dellwig, Olaf and Pinkerneil, Sylvia and Brauer, Achim and Dittmann, Elke and Wagner, Dirk and Liebner, Susanne},
  title     = {From water into sediment-tracing freshwater cyanobacteria via DNA analyses},
  series = {Microorganisms : open access journal},
  volume    = {9},
  journal   = {Microorganisms : open access journal},
  number    = {8},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2076-2607},
  doi       = {10.3390/microorganisms9081778},
  pages     = {20},
  year      = {2021},
  abstract  = {Sedimentary ancient DNA-based studies have been used to probe centuries of climate and environmental changes and how they affected cyanobacterial assemblages in temperate lakes. Due to cyanobacteria containing potential bloom-forming and toxin-producing taxa, their approximate reconstruction from sediments is crucial, especially in lakes lacking long-term monitoring data. To extend the resolution of sediment record interpretation, we used high-throughput sequencing, amplicon sequence variant (ASV) analysis, and quantitative PCR to compare pelagic cyanobacterial composition to that in sediment traps (collected monthly) and surface sediments in Lake Tiefer See. Cyanobacterial composition, species richness, and evenness was not significantly different among the pelagic depths, sediment traps and surface sediments (p > 0.05), indicating that the cyanobacteria in the sediments reflected the cyanobacterial assemblage in the water column. However, total cyanobacterial abundances (qPCR) decreased from the metalimnion down the water column. The aggregate-forming (Aphanizomenon) and colony-forming taxa (Snowella) showed pronounced sedimentation. In contrast, Planktothrix was only very poorly represented in sediment traps (meta- and hypolimnion) and surface sediments, despite its highest relative abundance at the thermocline (10 m water depth) during periods of lake stratification (May-October). We conclude that this skewed representation in taxonomic abundances reflects taphonomic processes, which should be considered in future DNA-based paleolimnological investigations.},
  language  = {en}
}
@article{ReynaGonzalezSchmidPetrasetal.2016,
  author    = {Reyna-Gonz{\´a}lez, Emmanuel and Schmid, Bianca and Petras, Daniel and S{\"u}ssmuth, Roderich D. and Dittmann, Elke},
  title     = {Leader Peptide-Free In Vitro Reconstitution of Microviridin Biosynthesis Enables Design of Synthetic Protease-Targeted Libraries},
  series = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition},
  volume    = {55},
  journal   = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1433-7851},
  doi       = {10.1002/anie.201604345},
  pages     = {9398 -- 9401},
  year      = {2016},
  abstract  = {Microviridins are a family of ribosomally synthesized and post-translationally modified peptides with a highly unusual architecture featuring non-canonical lactone as well as lactam rings. Individual variants specifically inhibit different types of serine proteases. Here we have established an efficient in vitro reconstitution approach based on two ATP-grasp ligases that were constitutively activated using covalently attached leader peptides and a GNAT-type N-acetyltransferase. The method facilitates the efficient in vitro one-pot transformation of microviridin core peptides to mature microviridins. The engineering potential of the chemo-enzymatic technology was demonstrated for two synthetic peptide libraries that were used to screen and optimize microviridin variants targeting the serine proteases trypsin and subtilisin. Successive analysis of intermediates revealed distinct structure-activity relationships for respective target proteases.},
  language  = {en}
}
@article{SchuurmansBrinkmannMakoweretal.2018,
  author    = {Schuurmans, Jasper Merijn and Brinkmann, Bregje W. and Makower, Katharina and Dittmann, Elke and Huisman, Jef and Matthijs, Hans C. P.},
  title     = {Microcystin interferes with defense against high oxidative stress in harmful cyanobacteria},
  series = {Harmful algae},
  volume    = {78},
  journal   = {Harmful algae},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {1568-9883},
  doi       = {10.1016/j.hal.2018.07.008},
  pages     = {47 -- 55},
  year      = {2018},
  abstract  = {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.},
  language  = {en}
}
@article{HuLudsinMartinetal.2018,
  author    = {Hu, Chenlin and Ludsin, Stuart A. and Martin, Jay F. and Dittmann, Elke and Lee, Jiyoung},
  title     = {Mycosporine-like amino acids (MAAs)-producing Microcystis in Lake Erie},
  series = {Harmful algae},
  volume    = {77},
  journal   = {Harmful algae},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {1568-9883},
  doi       = {10.1016/j.hal.2018.05.010},
  pages     = {1 -- 10},
  year      = {2018},
  abstract  = {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.},
  language  = {en}
}
@article{BarchewitzGuljamowMeissneretal.2019,
  author    = {Barchewitz, Tino and Guljamow, Arthur and Meißner, Sven and Timm, Stefan and Henneberg, Manja and Baumann, Otto and Hagemann, Martin and Dittmann, Elke},
  title     = {Non-canonical localization of RubisCO under high-light conditions in the toxic cyanobacterium Microcystis aeruginosa PCC7806},
  series = {Environmental microbiology},
  volume    = {21},
  journal   = {Environmental microbiology},
  number    = {12},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1462-2912},
  doi       = {10.1111/1462-2920.14837},
  pages     = {4836 -- 4851},
  year      = {2019},
  abstract  = {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.},
  language  = {en}
}