TY - JOUR A1 - Kehr, Jan-Christoph A1 - Picchi, Douglas Gatte A1 - Dittmann-Thünemann, Elke T1 - Natural product biosyntheses in cyanobacteria a treasure trove of unique enzymes JF - Beilstein journal of organic chemistry N2 - Cyanobacteria are prolific producers of natural products. Investigations into the biochemistry responsible for the formation of these compounds have revealed fascinating mechanisms that are not, or only rarely, found in other microorganisms. In this article, we survey the biosynthetic pathways of cyanobacteria isolated from freshwater, marine and terrestrial habitats. We especially emphasize modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) pathways and highlight the unique enzyme mechanisms that were elucidated or can be anticipated for the individual products. We further include ribosomal natural products and UV-absorbing pigments from cyanobacteria. Mechanistic insights obtained from the biochemical studies of cyanobacterial pathways can inspire the development of concepts for the design of bioactive compounds by synthetic-biology approaches in the future. KW - cyanobacteria KW - natural products KW - NRPS KW - PKS KW - ribosomal peptides Y1 - 2011 U6 - https://doi.org/10.3762/bjoc.7.191 SN - 1860-5397 VL - 7 IS - 2 SP - 1622 EP - 1635 PB - Beilstein-Institut zur Förderung der Chemischen Wissenschaften CY - Frankfurt, Main ER - TY - JOUR A1 - Weiz, Annika R. A1 - Ishida, Keishi A1 - Quitterer, Felix A1 - Meyer, Sabine A1 - Kehr, Jan-Christoph A1 - Mueller, Kristian M. A1 - Groll, Michael A1 - Hertweck, Christian A1 - Dittmann-Thünemann, Elke T1 - Harnessing the evolvability of tricyclic microviridins to dissect protease-inhibitor interactions JF - Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition N2 - Understanding and controlling proteolysis is an important goal in therapeutic chemistry. Among the natural products specifically inhibiting proteases microviridins are particularly noteworthy. Microviridins are ribosomally produced and posttranslationally modified peptides that are processed into a unique, cagelike architecture. Here, we report a combined rational and random mutagenesis approach that provides fundamental insights into selectivity-conferring moieties of microviridins. The potent variant microviridin J was co-crystallized with trypsin, and for the first time the three-dimensional structure of microviridins was determined and the mode of inhibition revealed. KW - cyanobacteria KW - peptide engineering KW - protease inhibitors KW - RiPPs KW - structure elucidation Y1 - 2014 U6 - https://doi.org/10.1002/anie.201309721 SN - 1433-7851 SN - 1521-3773 VL - 53 IS - 14 SP - 3735 EP - 3738 PB - Wiley-VCH CY - Weinheim ER - TY - GEN A1 - Kehr, Jan-Christoph A1 - Dittmann-Thünemann, Elke T1 - Biosynthesis and function of extracellular glycans in cyanobacteria N2 - The cell surface of cyanobacteria is covered with glycans that confer versatility and adaptability to a multitude of environmental factors. The complex carbohydrates act as barriers against different types of stress and play a role in intra- as well as inter-species interactions. In this review, we summarize the current knowledge of the chemical composition, biosynthesis and biological function of exo- and lipo-polysaccharides from cyanobacteria and give an overview of sugar-binding lectins characterized from cyanobacteria. We discuss similarities with well-studied enterobacterial systems and highlight the unique features of cyanobacteria. We pay special attention to colony formation and EPS biosynthesis in the bloom-forming cyanobacterium, Microcystis aeruginosa. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 346 KW - cyanobacteria KW - exopolysaccharides KW - lipopolysaccharides KW - colony formation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-400121 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 -