@article{GattePicchiWeizIshidaetal.2014,
  author    = {Gatte-Picchi, Douglas and Weiz, Annika and Ishida, Keishi and Hertweck, Christian and Dittmann-Th{\"u}nemann, Elke},
  title     = {Functional analysis of environmental DNA-derived microviridins provides new insights into the diversity of the tricyclic peptide family},
  series = {Applied and environmental microbiology},
  volume    = {80},
  journal   = {Applied and environmental microbiology},
  number    = {4},
  publisher = {American Society for Microbiology},
  address   = {Washington},
  issn      = {0099-2240},
  doi       = {10.1128/AEM.03502-13},
  pages     = {1380 -- 1387},
  year      = {2014},
  abstract  = {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.},
  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}
}