38075
2014
2014
eng
1380
1387
8
4
80
article
American Society for Microbiology
Washington
1
--
--
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Functional analysis of environmental DNA-derived microviridins provides new insights into the diversity of the tricyclic peptide family
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.
Applied and environmental microbiology
10.1128/AEM.03502-13
24334668
0099-2240
1098-5336
wos:2014
WOS:000331625100017
Dittmann, E (reprint author), Univ Potsdam, Inst Biochem & Biol, Dept Microbiol, Potsdam, Germany., editt@uni-potsdam.de
National Council for Scientific and Technological Development (CNPq);
German Research Foundation (DFG) [Di910/4-1, He3469/4-1]
Douglas Gatte-Picchi
Annika Weiz
Keishi Ishida
Christian Hertweck
Elke Dittmann-Thünemann
Institut für Biochemie und Biologie
Referiert
37943
2014
2014
eng
3735
3738
4
14
53
article
Wiley-VCH
Weinheim
1
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Harnessing the evolvability of tricyclic microviridins to dissect protease-inhibitor interactions
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.
Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition
10.1002/anie.201309721
24591244
1433-7851
1521-3773
wos:2014
WOS:000337176800022
Dittmann, E (reprint author), Univ Potsdam, Inst Biochem & Biol, Karl Liebknecht Str 24-25, D-14476 Potsdam, Germany., editt@uni-potsdam.de
German Research foundation (DFG) [Di910/4-1, He3469/4-1]; grant in the
cluster of excellence UniCAT
Annika R. Weiz
Keishi Ishida
Felix Quitterer
Sabine Meyer
Jan-Christoph Kehr
Kristian M. Mueller
Michael Groll
Christian Hertweck
Elke Dittmann-Thünemann
eng
uncontrolled
cyanobacteria
eng
uncontrolled
peptide engineering
eng
uncontrolled
protease inhibitors
eng
uncontrolled
RiPPs
eng
uncontrolled
structure elucidation
Institut für Biochemie und Biologie
Referiert