Journalartikel

Jahr der Veröffentlichung: 2018

Seiten: 836-840

Zeitschrift: Angewandte Chemie International Edition

Bandnummer: 57

Heftnummer: 3

ISSN: 1433-7851

DOI Link: https://doi.org/10.1002/anie.201707996

Verlag: Wiley

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.

Harvard-Zitierstil: Crüsemann, M., Reher, R., Schamari, I., Brachmann, A., Ohbayashi, T., Kuschak, M., et al. (2018) Heterologous Expression, Biosynthetic Studies, and Ecological Function of the Selective Gq-Signaling Inhibitor FR900359, Angewandte Chemie International Edition, 57(3), pp. 836-840. https://doi.org/10.1002/anie.201707996

APA-Zitierstil: Crüsemann, M., Reher, R., Schamari, I., Brachmann, A., Ohbayashi, T., Kuschak, M., Malfacini, D., Seidinger, A., Pinto-Carbo, M., Richarz, R., Reuter, T., Kehraus, S., Hallab, A., Attwood, M., Schiöth, H., Mergaert, P., Kikuchi, Y., Schäberle, T., Kostenis, E., ...König, G. (2018). Heterologous Expression, Biosynthetic Studies, and Ecological Function of the Selective Gq-Signaling Inhibitor FR900359. Angewandte Chemie International Edition. 57(3), 836-840. https://doi.org/10.1002/anie.201707996