TY - JOUR A1 - Arnison, Paul G. A1 - Bibb, Mervyn J. A1 - Bierbaum, Gabriele A1 - Bowers, Albert A. A1 - Bugni, Tim S. A1 - Bulaj, Grzegorz A1 - Camarero, Julio A. A1 - Campopiano, Dominic J. A1 - Challis, Gregory L. A1 - Clardy, Jon A1 - Cotter, Paul D. A1 - Craik, David J. A1 - Dawson, Michael A1 - Dittmann-Thünemann, Elke A1 - Donadio, Stefano A1 - Dorrestein, Pieter C. A1 - Entian, Karl-Dieter A1 - Fischbach, Michael A. A1 - Garavelli, John S. A1 - Goeransson, Ulf A1 - Gruber, Christian W. A1 - Haft, Daniel H. A1 - Hemscheidt, Thomas K. A1 - Hertweck, Christian A1 - Hill, Colin A1 - Horswill, Alexander R. A1 - Jaspars, Marcel A1 - Kelly, Wendy L. A1 - Klinman, Judith P. A1 - Kuipers, Oscar P. A1 - Link, A. James A1 - Liu, Wen A1 - Marahiel, Mohamed A. A1 - Mitchell, Douglas A. A1 - Moll, Gert N. A1 - Moore, Bradley S. A1 - Mueller, Rolf A1 - Nair, Satish K. A1 - Nes, Ingolf F. A1 - Norris, Gillian E. A1 - Olivera, Baldomero M. A1 - Onaka, Hiroyasu A1 - Patchett, Mark L. A1 - Piel, Jörn A1 - Reaney, Martin J. T. A1 - Rebuffat, Sylvie A1 - Ross, R. Paul A1 - Sahl, Hans-Georg A1 - Schmidt, Eric W. A1 - Selsted, Michael E. A1 - Severinov, Konstantin A1 - Shen, Ben A1 - Sivonen, Kaarina A1 - Smith, Leif A1 - Stein, Torsten A1 - Suessmuth, Roderich D. A1 - Tagg, John R. A1 - Tang, Gong-Li A1 - Truman, Andrew W. A1 - Vederas, John C. A1 - Walsh, Christopher T. A1 - Walton, Jonathan D. A1 - Wenzel, Silke C. A1 - Willey, Joanne M. A1 - van der Donk, Wilfred A. T1 - Ribosomally synthesized and post-translationally modified peptide natural products overview and recommendations for a universal nomenclature JF - Natural product reports : a journal of current developments in bio-organic chemistry N2 - This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed. Y1 - 2013 U6 - https://doi.org/10.1039/c2np20085f SN - 0265-0568 VL - 30 IS - 1 SP - 108 EP - 160 PB - Royal Society of Chemistry CY - Cambridge 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 - 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 - 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 - Dittmann-Thünemann, Elke A1 - Fewer, David P. A1 - Neilan, Brett A. T1 - Cyanobacterial toxins biosynthetic routes and evolutionary roots JF - FEMS microbiology reviews N2 - Cyanobacteria produce an unparalleled variety of toxins that can cause severe health problems or even death in humans, and wild or domestic animals. In the last decade, biosynthetic pathways have been assigned to the majority of the known toxin families. This review summarizes current knowledge about the enzymatic basis for the production of the hepatotoxins microcystin and nodularin, the cytotoxin cylindrospermopsin, the neurotoxins anatoxin and saxitoxin, and the dermatotoxin lyngbyatoxin. Elucidation of the biosynthetic pathways of the toxins has paved the way for the development of molecular techniques for the detection and quantification of the producing cyanobacteria in different environments. Phylogenetic analyses of related clusters from a large number of strains has also allowed for the reconstruction of the evolutionary scenarios that have led to the emergence, diversification, and loss of such gene clusters in different strains and genera of cyanobacteria. Advances in the understanding of toxin biosynthesis and evolution have provided new methods for drinking-water quality control and may inspire the development of techniques for the management of bloom formation in the future. KW - microcystin KW - cylindrospermopsin KW - anatoxin KW - saxitoxin KW - cyanobacteria Y1 - 2013 U6 - https://doi.org/10.1111/j.1574-6976.2012.12000.x SN - 0168-6445 SN - 1574-6976 VL - 37 IS - 1 SP - 23 EP - 43 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Dittmann-Thünemann, Elke A1 - Gugger, Muriel A1 - Sivonen, Kaarina A1 - Fewer, David P. T1 - Natural Product Biosynthetic Diversity and Comparative Genomics of the Cyanobacteria JF - Trends in microbiology N2 - Cyanobacteria are an ancient lineage of slow-growing photosynthetic bacteria and a prolific source of natural products with intricate chemical structures and potent biological activities. The bulk of these natural products are known from just a handful of genera. Recent efforts have elucidated the mechanisms underpinning the biosynthesis of a diverse array of natural products from cyanobacteria. Many of the biosynthetic mechanisms are unique to cyanobacteria or rarely described from other organisms. Advances in genome sequence technology have precipitated a deluge of genome sequences for cyanobacteria. This makes it possible to link known natural products to biosynthetic gene clusters but also accelerates the discovery of new natural products through genome mining. These studies demonstrate that cyanobacteria encode a huge variety of cryptic gene clusters for the production of natural products, and the known chemical diversity is likely to be just a fraction of the true biosynthetic capabilities of this fascinating and ancient group of organisms. Y1 - 2015 U6 - https://doi.org/10.1016/j.tim.2015.07.008 SN - 0966-842X SN - 1878-4380 VL - 23 IS - 10 SP - 642 EP - 652 PB - Elsevier CY - Oxford 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 - Gatte-Picchi, Douglas A1 - Weiz, Annika A1 - Ishida, Keishi A1 - Hertweck, Christian A1 - Dittmann-Thünemann, Elke T1 - Functional analysis of environmental DNA-derived microviridins provides new insights into the diversity of the tricyclic peptide family JF - Applied and environmental microbiology N2 - Microviridins represent a unique family of ribosomally synthesized cage-like depsipeptides from cyanobacteria with potent protease-inhibitory activities. The natural diversity of these peptides is largely unexplored. Here, we describe two methodologies that were developed to functionally characterize cryptic microviridin gene clusters from metagenomic DNA. Environmental samples were collected and enriched from cyanobacterial freshwater blooms of different geographical origins containing predominantly Microcystis sp. Microviridins were produced either directly from fosmid clones or after insertion of environmental DNA-derived gene cassettes into a minimal expression platform in Escherichia coli. Three novel microviridin variants were isolated and tested against different serine-type proteases. The comparison of the bioactivity profiles of the new congeners allows deduction of further structure-function relationships for microviridins. Moreover, this study provides new insights into microviridin processing and gene cluster organization. Y1 - 2014 U6 - https://doi.org/10.1128/AEM.03502-13 SN - 0099-2240 SN - 1098-5336 VL - 80 IS - 4 SP - 1380 EP - 1387 PB - American Society for Microbiology CY - Washington ER - TY - JOUR A1 - Guljamow, Arthur A1 - Delissen, Friedmar A1 - Baumann, Otto A1 - Thuenemann, Andreas F. A1 - Dittmann-Thünemann, Elke T1 - Unique properties of eukaryote-type actin and profilin horizontally transferred to cyanobacteria JF - PLoS one N2 - A eukaryote-type actin and its binding protein profilin encoded on a genomic island in the cyanobacterium Microcystis aeruginosa PCC 7806 co-localize to form a hollow, spherical enclosure occupying a considerable intracellular space as shown by in vivo fluorescence microscopy. Biochemical and biophysical characterization reveals key differences between these proteins and their eukaryotic homologs. Small-angle X-ray scattering shows that the actin assembles into elongated, filamentous polymers which can be visualized microscopically with fluorescent phalloidin. Whereas rabbit actin forms thin cylindrical filaments about 100 mu m in length, cyanobacterial actin polymers resemble a ribbon, arrest polymerization at 510 lam and tend to form irregular multi-strand assemblies. While eukaryotic profilin is a specific actin monomer binding protein, cyanobacterial profilin shows the unprecedented property of decorating actin filaments. Electron micrographs show that cyanobacterial profilin stimulates actin filament bundling and stabilizes their lateral alignment into heteropolymeric sheets from which the observed hollow enclosure may be formed. We hypothesize that adaptation to the confined space of a bacterial cell devoid of binding proteins usually regulating actin polymerization in eukaryotes has driven the co-evolution of cyanobacterial actin and profilin, giving rise to an intracellular entity. Y1 - 2012 U6 - https://doi.org/10.1371/journal.pone.0029926 SN - 1932-6203 VL - 7 IS - 1 SP - 221 EP - 231 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Harel, Moshe A1 - Weiss, Gad A1 - Daniel, Einat A1 - Wilenz, Avraham A1 - Hadas, Ora A1 - Sukenik, Assaf A1 - Sedmak, Bojan A1 - Dittmann-Thünemann, Elke A1 - Braun, Sergei A1 - Kaplan, Aaron T1 - Casting a net fibres produced by Microcystis sp in field and laboratory populations JF - Environmental microbiology reports N2 - The reasons for the apparent dominance of the toxic cyanobacterium Microcystis sp., reflected by its massive blooms in many fresh water bodies, are poorly understood. We show that in addition to a large array of secondary metabolites, some of which are toxic to eukaryotes, Microcystis sp. secretes large amounts of fibrous exopolysaccharides that form extremely long fibres several millimetres in length. This phenomenon was detected in field and laboratory cultures of various Microcystis strains. In addition, we have identified and characterized three of the proteins associated with the fibres and the genes encoding them in Microcystis sp. PCC 7806 but were unable to completely delete them from its genome. Phylogenetic analysis of the most abundant one, designated IPF-469, showed its presence only in cyanobacteria. Its closest relatives were detected in Synechocystis sp. PCC 6803 and in Cyanothece sp. strains; in the latter the genomic organization of the IPF-469 was highly conserved. IPF-469 and the other two proteins identified here, a haloperoxidase and a haemolysin-type calcium-binding protein, may be part of the fibres secretion pathway. The biological role of the fibres in Microcystis sp. is discussed. Y1 - 2012 U6 - https://doi.org/10.1111/j.1758-2229.2012.00339.x SN - 1758-2229 VL - 4 IS - 3 SP - 342 EP - 349 PB - Wiley-Blackwell CY - Malden ER -