@phdthesis{Barchewitz2021,
  author    = {Barchewitz, Tino},
  title     = {Impact of microcystin on the non-canonical localization of RubisCO in the toxic bloom-forming cyanobacterium Microcystis aeruginosa PCC7806},
  doi       = {10.25932/publishup-50829},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-508299},
  school      = {Universit{\"a}t Potsdam},
  pages     = {vii, 106},
  year      = {2021},
  abstract  = {Cyanobacteria are an abundant bacterial group and are found in a variety of ecological niches all around the globe. They can serve as a real threat for fish or mammals and can restrict the use of lakes or rivers for recreational purposes or as a source of drinking water, when they form blooms. One of the most abundant bloom-forming cyanobacteria is Microcystis aeruginosa. In the first part of the study, the role and possible dynamics of RubisCO in M. aeruginosa during high-light irradiation were examined. Its response was analyzed on the protein and peptide level via immunoblotting, immunofluorescence microscopy and with high performance liquid chromatography (HPLC). It was revealed that large amounts of RubisCO were located outside of carboxysomes under the applied high light stress. RubisCO aggregated mainly underneath the cytoplasmic membrane. There it forms a putative Calvin-Benson-Bassham (CBB) super complex together with other enzymes of photosynthesis. This complex could be part of an alternative carbon-concentrating mechanism (CCM) in M. aeruginosa, which enables a faster, and energy saving adaptation to high light stress of the whole bloom. Furthermore, the re-localization of RubisCO was delayed in the microcystin-deficient mutant ΔmcyB and RubisCO was more evenly distributed over the cell in comparison to the wild type. Since ΔmcyB is not harmed in its growth, possibly other produced cyanopeptides as aeruginosin or cyanopeptolin also play a role in the stabilization of RubisCO and the putative CBB complex, especially in the microcystin-free mutant. In the second part of this work, the possible role of microcystin as an extracellular signaling peptide during the diurnal cycle was studied. HPLC analysis showed a strong increase of extracellular microcystin in the wild type when the population entered nighttime and it resumed into the next day as well. Together with the increase of extracellular microcystin, a strong decrease of protein-bound intracellular microcystin was observed via immunoblot analysis. Interestingly, the signal of the large subunit of RubisCO (RbcL) also diminished when high amounts of microcystin were present in the surrounding medium. Microcystin addition experiments to M. aeruginosa WT and ΔmcyB cultures support this observation, since the immunoblot signal of both subunits of RubisCO and CcmK, a shell protein of carboxysomes, diminished after the addition of microcystin. In addition, the fluctuation of cyanopeptolin during the diurnal cycle indicates a more prominent role of other cyanopeptides besides microcystin as a signaling peptide, intracellularly as well as extracellularly.},
  language  = {en}
}
@article{BatistaWoodhouseGrossartetal.2018,
  author    = {Batista, A. M. M. and Woodhouse, Jason Nicholas and Grossart, Hans-Peter and Giani, A.},
  title     = {Methanogenic archaea associated to Microcystis sp. in field samples and in culture},
  series = {Hydrobiologia : acta hydrobiologica, hydrographica, limnologica et protistologica},
  volume    = {831},
  journal   = {Hydrobiologia : acta hydrobiologica, hydrographica, limnologica et protistologica},
  number    = {1},
  publisher = {Springer},
  address   = {Dordrecht},
  issn      = {0018-8158},
  doi       = {10.1007/s10750-018-3655-3},
  pages     = {163 -- 172},
  year      = {2018},
  abstract  = {Cyanobacterial mass developments impact the community composition of heterotrophic microorganisms with far-reaching consequences for biogeochemical and energy cycles of freshwater ecosystems including reservoirs. Here we sought to evaluate the temporal stability of methanogenic archaea in the water column and further scrutinize their associations with cyanobacteria. Monthly samples were collected from October 2009 to December 2010 in hypereutrophic Pampulha reservoir with permanently blooming cyanobacteria, and from January to December 2011 in oligotrophic Volta Grande reservoir with only sporadic cyanobacteria incidence. The presence of archaea in cyanobacterial cultures was investigated by screening numerous strains of Microcystis spp. from these reservoirs as well as from lakes in Europe, Asia, and North-America. We consistently determined the occurrence of archaea, in particular methanogenic archaea, in both reservoirs throughout the year. However, archaea were only associated with two strains (Microcystis sp. UFMG 165 and UFMG 175) recently isolated from these reservoirs. These findings do not implicate archaea in the occurrence of methane in the epilimnion of inland waters, but rather serve to highlight the potential of microhabitats associated with particles, including phytoplankton, to shelter unique microbial communities.},
  language  = {en}
}
@phdthesis{Dehm2020,
  author    = {Dehm, Daniel},
  title     = {Development of concepts for the genomic mining of novel secondary metabolites in symbiotic cyanobacteria},
  doi       = {10.25932/publishup-47834},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-478342},
  school      = {Universit{\"a}t Potsdam},
  pages     = {VIII, 122, XII},
  year      = {2020},
  abstract  = {Naturstoffe sind seit der goldenen {\"A}ra der Antibiotika von immer gr{\"o}ßerem Interesse, sowohl f{\"u}r die Grundlagenforschung als auch die Angewandten Wissenschaften, da sie die Hauptquelle f{\"u}r neuartige Pharmazeutika mit starken antibiotischen, anti-entz{\"u}ndlichen und Antitumor-Aktivit{\"a}ten darstellen. Neben den technologischen Fortschritten im Bereich der Hochdurchsatz Genomsequenzierung und dem verbesserten Verst{\"a}ndnis des modularen Aufbaus der Biosynthesewege von Sekund{\"a}rmetaboliten, kam es auch zu einem Wechsel vom labor-gest{\"u}tzten Screening aktiver Zellextrakte hin zum Algorithmen-basierten in silico Screening nach neuen Naturstoff-Biosyntheseclustern. Obwohl die steigende Zahl verf{\"u}gbarer Genomsequenzen zeigte, dass nicht-ribosomale Peptid-Synthetasen (NRPS), Polyketid-Synthasen (PKS), und ribosomal synthetisierte und posttranslational modifizierte Peptide (RiPPs) ubiquit{\"a}r in allen Sparten des Lebens gefunden werden k{\"o}nnen, so zeigen einige Phyla wie Actinobakterien oder Cyanobakterien eine besonders hohe Dichte an Sekund{\"a}rmetabolitclustern. Der fakultativ symbiotische, N2-fixierende Modellorganismus N. punctiforme PCC73102 ist ein terrestrisches typ-IV Cyanobakterium, welches nicht nur einen besonders hohen Anteil seines Genoms der Produktion von Sekund{\"a}rmetaboliten widmet, sondern zus{\"a}tzlich noch genetisch modifizierbar ist. Eine AntiSMASH Analyse des Genoms zeigte, dass N. punctiforme insgesamt sechzehn potentielle Sekund{\"a}rmetabolitcluster besitzt, von denen aber bis heute nur zweien ein spezifisches Produkt zugewiesen werden konnte. Das macht N. punctiforme zu einem perfekten Testorganismus f{\"u}r die Entwicklung eines neuartigen kombinatorischen Genomic Mining Ansatzes zur Detektion von bislang unbeschriebenen Naturstoffen. Der neuartige Ansatz, der im Rahmen dieser Studie entwickelt wurde, stellt eine Kombination aus Genomic Mining, unabh{\"a}ngigen Monitoring-Techniken sowie modifizierten Kultivierungsbedingungen dar und f{\"u}hrte nicht nur zu neuen Erkenntnissen im Bereich cyanobakterieller Naturstoffsynthese, sondern letztlich auch zur Entdeckung eines neuen, von N. punctiforme produzierten, Naturstoffs. Die Herstellung und Untersuchung einer Reporterstamm Bibliothek, bestehend aus je einem CFP-produzierenden Transkriptionsreporter f{\"u}r jedes der sechzehn Sekund{\"a}rmetabolitcluster von N. punctiforme, zeigte, dass im Gegensatz zur Erwartung nicht alle Biosynthesecluster f{\"u}r die man kein Produkt nachweisen kann auch nicht exprimiert werden. Stattdessen konnten klar definierbare Expressionsmuster beschrieben werden, was deutlich machte, dass die Naturstoffproduktion einer engen Regulation unterliegt und nur ein kleiner Teil der Biosynthesecluster unter Standardbedingungen tats{\"a}chlich still sind. Dar{\"u}ber hinaus f{\"u}hrte die Erh{\"o}hung der Lichtintensit{\"a}t sowie der Kohlenstoffdioxid-Verf{\"u}gbarkeit zusammen mit der Kultivierung von N. punctiforme zu extrem hohen Zelldichten zu einer starken Erh{\"o}hung der gesamten metabolischen Aktivit{\"a}t des Organismus. N{\"a}here Untersuchungen der Zellextrakte dieser hoch-dichte Kultivierungen f{\"u}hrten letztlich zur Entdeckung einer neuartigen Gruppe von Microviridinen mit verl{\"a}ngerter Peptidsequenz, welche Microviridin N3-N9 genannt wurden. Sowohl die Kultivierung der Transkriptionsreporter als auch die RTqPCR-basierte Untersuchung der Transkriptionslevel der verschiedenen Biosynthesecluster zeigten, dass die hoch-Zelldichte Kultivierung von N. punctiforme zu einer Aktivierung von 50\% der vorhandenen Sekund{\"a}rmetabolitcluster f{\"u}hrt. Im Gegensatz zu dieser sehr breit-gef{\"a}cherten Aktivierung, f{\"u}hrt die Co-Kultivierung von N. punctiforme in chemischen oder physischen Kontakt zu einer N-gehungerten Wirtspflanze (Blasia pusilla) zu einer sehr spezifischen Aktivierung der RIPP4 und RiPP3 Biosynthesecluster. Obwohl dieser Effekt mittels verschiedener unabh{\"a}ngiger Methoden best{\"a}tigt werden konnte und trotz intensiver Analysebem{\"u}hungen, konnte jedoch keinem der beiden Cluster ein Produkt zugeordnet werden. Diese Studie stellt die erste weitreichende, systematische Analyse eines cyanobakteriellen Sekund{\"a}rmetaboloms durch einen kombinatorischen Ansatz aus Genomic Mining und unabh{\"a}ngigen Monitoring-Techniken dar und kann als neue strategische Herangehensweise f{\"u}r die Untersuchung anderer Organismen hinsichtlich ihrer Sekund{\"a}rmetabolit-Produktion dienen. Obwohl es bereits gut beschriebene einzelne Sekund{\"a}rmetabolite gibt, wie beispielweise den Zelldifferenzierungsfaktor PatS in Anabaena sp. PCC7120, so ist der Grad an Regulation der in dieser Studie gezeigt werden konnte bislang beispiellos und die Entschl{\"u}sselung dieser Mechanismen k{\"o}nnte die Entdeckung neuer Naturstoffe stark beschleunigen. Daneben lassen die Ergebnisse aber auch darauf schließen, dass die Induktion der Biosynthesewege nicht das eigentliche Problem darstellt, sondern vielmehr die verl{\"a}ssliche Detektion deren Produkte. Die Erarbeitung neuer Analytik-Strategien k{\"o}nnte somit auch einen deutlichen Einfluss auf die Geschwindigkeit der Entdeckung neuer Naturstoffe haben.},
  language  = {en}
}
@article{FrijiaForknerMinisinietal.2019,
  author    = {Frijia, Gianluca and Forkner, R. and Minisini, D. and Pacton, M. and Struck, Ulrich and Mutti, Maria},
  title     = {Cyanobacteria proliferation in the cenomanian-turonian boundary interval of the apennine carbonate platform:},
  series = {Geochemistry, geophysics, geosystems},
  volume    = {20},
  journal   = {Geochemistry, geophysics, geosystems},
  number    = {6},
  publisher = {American Geophysical Union},
  address   = {Washington},
  issn      = {1525-2027},
  doi       = {10.1029/2019GC008306},
  pages     = {2698 -- 2716},
  year      = {2019},
  abstract  = {Oceanic Anoxic Event-2 (OAE-2; Cenomanian-Turonian) is characterized by extensive deposition of organic carbon-rich deposits (black shales) in ocean basins worldwide as result of a major perturbation of the global carbon cycle. While the sedimentological, geochemical, and paleontological aspects of deep water expressions of OAE-2 have been intensively studied in the last few decades, much less attention has been given to the coeval shallow water deposits. In this study, we present the results of a detailed facies and petrographic (optical microscope and scanning electron microscopy) and geochemical studies (delta C-13(carb), delta C-13 (org), delta N-15(bulk), TOC, and Rock-Eval pyrolysis) on two key shallow marine sections from the Apennine Carbonate Platform (ACP; Italy). Here a continuous record of shallow water carbonates through the OAE-2 interval is preserved, offering the unique opportunity to document the archive of paleoenvironmental changes in a neritic setting, at a tropical latitude and far from the influence of a large continental block. Two conspicuous intervals are characterized by abundant and closely spaced dark microbial laminites found at correlative stratigraphic horizons in the two stratigraphic sections. These laminites contain elevated concentrations of TOC (up to 1\%) relative to microbial capping cycles laminites stratigraphically above and below. The organic matter preserved in these fine-grained laminites is dominated by cyanobacteria remains, which accounted for most of the organic matter produced on the ACP in these intervals. Our study suggests that Tethyan carbonate platforms experienced significant biological changes during OAE-2, alternating, in few kiloyears, between eutrophic phases dominated by microbial communities and mesotrophic/oligotrophic conditions favoring normal carbonate production/sedimentation. The synchronous occurrence of microbialite facies at different locations across the ACP and on other platforms worldwide (e.g., Mexico and Croatia) suggests a causal link between Large Igneous Province volcanism and the environmental conditions necessary to trigger cyanobacterial proliferation on shallow carbonate platforms.},
  language  = {en}
}
@misc{KoussoroplisSchwarzenbergerWacker2017,
  author    = {Koussoroplis, Apostolos-Manuel and Schwarzenberger, Anke and Wacker, Alexander},
  title     = {Diet quality determines lipase gene expression and lipase/esterase activity in Daphnia pulex},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-395661},
  pages     = {7},
  year      = {2017},
  abstract  = {We studied the short- (12 h) and long-term (144 h) response of Daphnia pulex lipases to quality shifts in diets consisting of different mixtures of the green alga Scenedesmus with the cyanobacterium Synechococcus, two species with contrasting lipid compositions. The lipase/esterase activity in both the gut and the body tissues had fast responses to the diet shift and increased with higher dietary contributions of Synechococcus. When screening the Daphnia genome for TAG lipases, we discovered a large gene-family expansion of these enzymes. We used a subset of eight genes for mRNA expression analyses and distinguished between influences of time and diet on the observed gene expression patterns. We identified five diet-responsive lipases of which three showed a sophisticated short- and long-term pattern of expression in response to small changes in food-quality. Furthermore, the gene expression of one of the lipases was strongly correlated to lipase/esterase activity in the gut suggesting its potentially major role in digestion. These findings demonstrate that the lipid-related enzymatic machinery of D. pulex is finely tuned to diet and might constitute an important mechanism of physiological adaptation in nutritionally complex environments.},
  language  = {en}
}
@article{KoussoroplisSchwarzenbergerWacker2017,
  author    = {Koussoroplis, Apostolos-Manuel and Schwarzenberger, Anke and Wacker, Alexander},
  title     = {Diet quality determines lipase gene expression and lipase/esterase activity in Daphnia pulex},
  series = {Biology open : BiO},
  volume    = {6},
  journal   = {Biology open : BiO},
  publisher = {The company of Biologists},
  address   = {Cambridge},
  doi       = {10.1242/bio.022046},
  pages     = {210 -- 216},
  year      = {2017},
  abstract  = {We studied the short- (12 h) and long-term (144 h) response of Daphnia pulex lipases to quality shifts in diets consisting of different mixtures of the green alga Scenedesmus with the cyanobacterium Synechococcus, two species with contrasting lipid compositions. The lipase/esterase activity in both the gut and the body tissues had fast responses to the diet shift and increased with higher dietary contributions of Synechococcus. When screening the Daphnia genome for TAG lipases, we discovered a large gene-family expansion of these enzymes. We used a subset of eight genes for mRNA expression analyses and distinguished between influences of time and diet on the observed gene expression patterns. We identified five diet-responsive lipases of which three showed a sophisticated short- and long-term pattern of expression in response to small changes in food-quality. Furthermore, the gene expression of one of the lipases was strongly correlated to lipase/esterase activity in the gut suggesting its potentially major role in digestion. These findings demonstrate that the lipid-related enzymatic machinery of D. pulex is finely tuned to diet and might constitute an important mechanism of physiological adaptation in nutritionally complex environments.},
  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{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}
}
@misc{PearsonDittmannMazmouzetal.2016,
  author    = {Pearson, Leanne A. and Dittmann, Elke and Mazmouz, Rabia and Ongley, Sarah E. and Neilan, Brett A.},
  title     = {The genetics, biosynthesis and regulation of toxic specialized metabolites of cyanobacteria},
  series = {Harmful algae},
  volume    = {54},
  journal   = {Harmful algae},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {1568-9883},
  doi       = {10.1016/j.hal.2015.11.002},
  pages     = {98 -- 111},
  year      = {2016},
  abstract  = {The production of toxic metabolites by cyanobacterial blooms represents a significant threat to the health of humans and ecosystems worldwide. Here we summarize the current state of the knowledge regarding the genetics, biosynthesis and regulation of well-characterized cyanotoxins, including the microcystins, nodularin, cylindrospermopsin, saxitoxins and antitoxins, as well as the lesser-known marine toxins (e.g. lyngbyatoxin, aplysiatoxin, jamaicamides, barbamide, curacin, hectochlorin and apratoxins). (C) 2015 Elsevier B.V. All rights reserved.},
  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}
}