Advanced search
1 file | 1.92 MB Add to list

Heterologous expression, biosynthetic studies and ecological function of the selective Gq-signaling inhibitor FR900359

Author
Organization
Abstract
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 invivo 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 invitro 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.
Keywords
biosynthesis, FR900359, Gproteins, heterologous expression, natural products, CHROMOBACTERIUM SP QS3666, ARDISIA-CRENATA SIMS, ANTIBIOTIC BIOSYNTHESIS, CYCLIC DEPSIPEPTIDE, STRUCTURAL BASIS, PROTEIN, PATHWAY, YM-254890, SYMBIONT

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 1.92 MB

Citation

Please use this url to cite or link to this publication:

MLA
Crüsemann, Max, Raphael Reher, Isabella Schamari, et al. “Heterologous Expression, Biosynthetic Studies and Ecological Function of the Selective Gq-signaling Inhibitor FR900359.” ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 57.3 (2018): 836–840. Print.
APA
Crüsemann, M., Reher, R., Schamari, I., Brachmann, A. O., Ohbayashi, T., Kuschak, M., Malfacini, D., et al. (2018). Heterologous expression, biosynthetic studies and ecological function of the selective Gq-signaling inhibitor FR900359. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 57(3), 836–840.
Chicago author-date
Crüsemann, Max, Raphael Reher, Isabella Schamari, Alexander O Brachmann, Tsubasa Ohbayashi, Markus Kuschak, Davide Malfacini, et al. 2018. “Heterologous Expression, Biosynthetic Studies and Ecological Function of the Selective Gq-signaling Inhibitor FR900359.” Angewandte Chemie-international Edition 57 (3): 836–840.
Chicago author-date (all authors)
Crüsemann, Max, Raphael Reher, Isabella Schamari, Alexander O Brachmann, Tsubasa Ohbayashi, Markus Kuschak, Davide Malfacini, Alexander Seidinger, Marta Pinto-Carbó, René Richarz, Tatjana Reuter, Stefan Kehraus, Asis Hallab, Misty Attwood, Helgi B Schiöth, Peter Mergaert, Yoshitomo Kikuchi, Till F Schäberle, Evi Kostenis, Daniela Wenzel, Christa E Müller, Jörn Piel, Aurélien Carlier, Leo Eberl, and Gabriele Maria Koenig. 2018. “Heterologous Expression, Biosynthetic Studies and Ecological Function of the Selective Gq-signaling Inhibitor FR900359.” Angewandte Chemie-international Edition 57 (3): 836–840.
Vancouver
1.
Crüsemann M, Reher R, Schamari I, Brachmann AO, Ohbayashi T, Kuschak M, et al. Heterologous expression, biosynthetic studies and ecological function of the selective Gq-signaling inhibitor FR900359. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 2018;57(3):836–40.
IEEE
[1]
M. Crüsemann et al., “Heterologous expression, biosynthetic studies and ecological function of the selective Gq-signaling inhibitor FR900359,” ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, vol. 57, no. 3, pp. 836–840, 2018.
@article{8540268,
  abstract     = {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 invivo 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 invitro 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.},
  author       = {Crüsemann, Max and Reher, Raphael and Schamari, Isabella and Brachmann, Alexander O and Ohbayashi, Tsubasa and Kuschak, Markus and Malfacini, Davide and Seidinger, Alexander and Pinto-Carbó, Marta and Richarz, René and Reuter, Tatjana and Kehraus, Stefan and Hallab, Asis and Attwood, Misty and Schiöth, Helgi B and Mergaert, Peter and Kikuchi, Yoshitomo and Schäberle, Till F and Kostenis, Evi and Wenzel, Daniela and Müller, Christa E and Piel, Jörn and Carlier, Aurélien and Eberl, Leo and Koenig, Gabriele Maria},
  issn         = {1433-7851},
  journal      = {ANGEWANDTE CHEMIE-INTERNATIONAL EDITION},
  keywords     = {biosynthesis,FR900359,Gproteins,heterologous expression,natural products,CHROMOBACTERIUM SP QS3666,ARDISIA-CRENATA SIMS,ANTIBIOTIC BIOSYNTHESIS,CYCLIC DEPSIPEPTIDE,STRUCTURAL BASIS,PROTEIN,PATHWAY,YM-254890,SYMBIONT},
  language     = {eng},
  number       = {3},
  pages        = {836--840},
  title        = {Heterologous expression, biosynthetic studies and ecological function of the selective Gq-signaling inhibitor FR900359},
  url          = {http://dx.doi.org/10.1002/anie.201707996},
  volume       = {57},
  year         = {2018},
}

Altmetric
View in Altmetric