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Heterologous Expres...
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Crüsemann, MaxUniv Bonn, Inst Pharmazeut Biol, Bonn, Germany
(author)
Heterologous Expression, Biosynthetic Studies, and Ecological Function of the Selective Gq-Signaling Inhibitor FR900359
- Article/chapterEnglish2018
Publisher, publication year, extent ...
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John Wiley & Sons,2018
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Numbers
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LIBRIS-ID:oai:DiVA.org:uu-342249
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-342249URI
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https://doi.org/10.1002/anie.201707996DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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The cyclic depsipeptide FR900359 (FR), isolated from the tropical plant Ardisia crenata, is a strong and selective inhibitor of Gq proteins, making it an indispensable pharmacological tool to study Gq-related processes, as well as a promising drug candidate. Gq inhibition is a novel mode of action for defense chemicals and crucial for the ecological function of FR, as shown by in vivo experiments in mice, its affinity to insect Gq proteins, and insect toxicity studies. The uncultured endosymbiont of A. crenata was sequenced, revealing the FR nonribosomal peptide synthetase (frs) gene cluster. We here provide a detailed model of FR biosynthesis, supported by in vitro enzymatic and bioinformatic studies, and the novel analogue AC-1, which demonstrates the flexibility of the FR starter condensation domains. Finally, expression of the frs genes in E. coli led to heterologous FR production in a cultivable, bacterial host for the first time.
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Reher, Raphael
(author)
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Schamari, IsabellaUniv Bonn, Inst Pharmazeut Biol, Bonn, Germany
(author)
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Brachmann, Alexander O] Eidgenoss Tech Hsch ETH Zurich, Inst Mikrobiol, Zurich, Switzerland
(author)
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Ohbayashi, TsubasaUniv Paris Sud, CEA, Gif Sur Yvette, France
(author)
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Kuschak, Markus
(author)
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Malfacini, Davide
(author)
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Seidinger, Alexander
(author)
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Pinto-Carbó, Marta
(author)
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Richarz, René
(author)
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Reuter, Tatjana
(author)
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Kehraus, Stefan
(author)
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Hallab, Asis
(author)
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Attwood, Misty M.Uppsala universitet,Funktionell farmakologi(Swepub:uu)misat949
(author)
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Schiöth, Helgi B.Uppsala universitet,Funktionell farmakologi(Swepub:uu)helgschi
(author)
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Mergaert, Peter
(author)
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Kikuchi, YoshitomoBioprod Res Inst AIST Hokkaido, Sapporo, Japan
(author)
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Schäberle, Till F
(author)
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Kostenis, Evi
(author)
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Wenzel, Daniela
(author)
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Müller, Christa E
(author)
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Piel, Jörn
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Carlier, AurélienUniv Ghent, Dept Biochem & Microbiol, Ghent, Belgium
(author)
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Eberl, Leo
(author)
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König, Gabriele M
(author)
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Univ Bonn, Inst Pharmazeut Biol, Bonn, GermanyUniv Bonn, Inst Pharmazeut Biol, Bonn, Germany
(creator_code:org_t)
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In:Angewandte Chemie International Edition: John Wiley & Sons57:3, s. 836-8401433-78511521-3773
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