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- Title
Identification of the Natural Product Rotihibin A as a TOR Kinase Signaling Inhibitor by Unbiased Transcriptional Profiling.
- Authors
Halder, Vivek; Oeljeklaus, Julian; Heilmann, Geronimo; Krahn, Jan H.; Liu, Yanlin; Xiong, Yan; Schlicht, Markus; Schillinger, Jasmin; Kracher, Barbara; Ehrmann, Michael; Kombrink, Erich; Kaschani, Farnusch; Kaiser, Markus
- Abstract
Abstract: Bioactive natural products are important starting points for developing chemical tools for biological research. For elucidating their bioactivity profile, biological systems with concise complexity such as cell culture systems are frequently used, whereas unbiased investigations in more complex multicellular systems are only rarely explored. Here, we demonstrate with the natural product Rotihibin A and the plant research model system Arabidopsis thaliana that unbiased transcriptional profiling enables a rapid, label‐free, and compound economic evaluation of a natural product′s bioactivity profile in a complex multicellular organism. To this end, we established a chemical synthesis of Rotihibin A as well as that of structural analogues, followed by transcriptional profiling‐guided identification and validation of Rotihibin A as a TOR signaling inhibitor (TOR=target of rapamycin). These findings illustrate that a combined approach of transcriptional profiling and natural product research may represent a technically simple approach to streamline the development of chemical tools from natural products even for biologically complex multicellular biological systems.
- Subjects
NATURAL products; BIOLOGICAL systems; CELL culture; ARABIDOPSIS thaliana; MULTICELLULAR organisms
- Publication
Chemistry - A European Journal, 2018, Vol 24, Issue 48, p12500
- ISSN
0947-6539
- Publication type
Article
- DOI
10.1002/chem.201802647