@phdthesis{Makower2016,
  author    = {Makower, Katharina},
  title     = {The roles of secondary metabolites in microcystis inter-strain interactions},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-93916},
  school      = {Universit{\"a}t Potsdam},
  pages     = {X, 131},
  year      = {2016},
  abstract  = {Among the bloom-forming and potentially harmful cyanobacteria, the genus Microcystis represents a most diverse taxon, on the genomic as well as on morphological and secondary metabolite levels. Microcystis communities are composed of a variety of diversified strains. The focus of this study lies on potential interactions between Microcystis representatives and the roles of secondary metabolites in these interaction processes. The role of secondary metabolites functioning as signaling molecules in the investigated interactions is demonstrated exemplary for the prevalent hepatotoxin microcystin. The extracellular and intracellular roles of microcystin are tested in microarray-based transcriptomic approaches. While an extracellular effect of microcystin on Microcystis transcription is confirmed and connected to a specific gene cluster of another secondary metabolite in this study, the intracellularly occurring microcystin is related with several pathways of the primary metabolism. A clear correlation of a microcystin knockout and the SigE-mediated regulation of carbon metabolism is found. According to the acquired transcriptional data, a model is proposed that postulates the regulating effect of microcystin on transcriptional regulators such as the alternative sigma factor SigE, which in return captures an essential role in sugar catabolism and redox-state regulation. For the purpose of simulating community conditions as found in the field, Microcystis colonies are isolated from the eutrophic lakes near Potsdam, Germany and established as stably growing under laboratory conditions. In co-habitation simulations, the recently isolated field strain FS2 is shown to specifically induce nearly immediate aggregation reactions in the axenic lab strain Microcystis aeruginosa PCC 7806. In transcriptional studies via microarrays, the induced expression program in PCC 7806 after aggregation induction is shown to involve the reorganization of cell envelope structures, a highly altered nutrient uptake balance and the reorientation of the aggregating cells to a heterotrophic carbon utilization, e.g. via glycolysis. These transcriptional changes are discussed as mechanisms of niche adaptation and acclimation in order to prevent competition for resources.},
  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{WeizIshidaMakoweretal.2011,
  author    = {Weiz, Annika R. and Ishida, Keishi and Makower, Katharina and Ziemert, Nadine and Hertweck, Christian and Dittmann-Th{\"u}nemann, Elke},
  title     = {Leader Peptide and a Membrane Protein Scaffold Guide the Biosynthesis of the Tricyclic Peptide Microviridin},
  series = {Chemistry \& biology},
  volume    = {18},
  journal   = {Chemistry \& biology},
  number    = {11},
  publisher = {Cell Press},
  address   = {Cambridge},
  issn      = {1074-5521},
  doi       = {10.1016/j.chembiol.2011.09.011},
  pages     = {1413 -- 1421},
  year      = {2011},
  abstract  = {Microviridins are unique protease inhibitors from bloom-forming cyanobacteria that have both ecological and pharmacological relevance. Their peptide backbones are produced ribosomally, and ATP grasp ligases introduce omega-ester and omega-amide bonds to yield rare cage-like structures. Bioinformatic analysis of the microviridin biosynthesis gene cluster suggests a novel type of processing machinery, which could rationalize the challenging in vivo/in vitro reconstitution of the pathway. In this work, we report the establishment of a minimal expression system for microviridins. Through bioinformatics and mutational analysis of the MdnA leader peptide we identified and characterized a strictly conserved binding motif that is specific for microviridin ligases. Furthermore, we showed that the ABC transporter MdnE is crucial for cyclization and processing of microviridins and demonstrated that MdnE is essential for stability of the microviridin biosynthesis complex.},
  language  = {en}
}