@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}
}
@article{WeizIshidaQuittereretal.2014,
  author    = {Weiz, Annika R. and Ishida, Keishi and Quitterer, Felix and Meyer, Sabine and Kehr, Jan-Christoph and Mueller, Kristian M. and Groll, Michael and Hertweck, Christian and Dittmann-Th{\"u}nemann, Elke},
  title     = {Harnessing the evolvability of tricyclic microviridins to dissect protease-inhibitor interactions},
  series = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition},
  volume    = {53},
  journal   = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition},
  number    = {14},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1433-7851},
  doi       = {10.1002/anie.201309721},
  pages     = {3735 -- 3738},
  year      = {2014},
  abstract  = {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.},
  language  = {en}
}
@article{PancraceIshidaBriandetal.2018,
  author    = {Pancrace, Claire and Ishida, Keishi and Briand, Enora and Pichi, Douglas Gatte and Weiz, Annika R. and Guljarmow, Arthur and Scalvenzi, Thibault and Sassoon, Nathalie and Hertweck, Christian and Dittmann, Elke and Gugger, Muriel},
  title     = {Unique Biosynthetic Pathway in Bloom-Forming Cyanobacterial Genus Microcystis Jointly Assembles Cytotoxic Aeruginoguanidines and Microguanidines},
  series = {ACS chemical biology},
  volume    = {14},
  journal   = {ACS chemical biology},
  number    = {1},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {1554-8929},
  doi       = {10.1021/acschembio.8b00918},
  pages     = {67 -- 75},
  year      = {2018},
  abstract  = {The cyanobacterial genus Microcystis is known to produce an elaborate array of structurally unique and biologically active natural products, including hazardous cyanotoxins. Cytotoxic aeruginoguanidines represent a yet unexplored family of peptides featuring a trisubstituted benzene unit and farnesylated arginine derivatives. In this study, we aimed at assigning these compounds to a biosynthetic gene cluster by utilizing biosynthetic attributes deduced from public genomes of Microcystis and the sporadic distribution of the metabolite in axenic strains of the Pasteur Culture Collection of Cyanobacteria. By integrating genome mining with untargeted metabolomics using liquid chromatography with mass spectrometry, we linked aeruginoguanidine (AGD) to a nonribosomal peptide synthetase gene cluster and coassigned a significantly smaller product to this pathway, microguanidine (MGD), previously only reported from two Microcystis blooms. Further, a new intermediate class of compounds named microguanidine amides was uncovered, thereby further enlarging this compound family. The comparison of structurally divergent AGDs and MGDs reveals an outstanding versatility of this biosynthetic pathway and provides insights into the assembly of the two compound subfamilies. Strikingly, aeruginoguanidines and microguanidines were found to be as widespread as the hepatotoxic microcystins, but the occurrence of both toxin families appeared to be mutually exclusive.},
  language  = {en}
}