Hybrid in silico/in vitro target fishing to assign function to “orphan” compounds of food origin: the case of the fungal metabolite atromentin

Dellafiora, Luca; Aichinger, Georg; Geib, Elena; Sánchez-Barrionuevo, Leyre; Brock, Matthias; Cánovas, David; Dall'Asta, Chiara; Marko, Doris

Abstract

Many small molecules of food origin may effect human health but lack an adequate description of their biological activity. To fill this knowledge gap, a first-line workflow is needed to assign putative functions, rank the endpoints for testing and guide wet-lab experiments. In this framework, the identification of potential biological targets can be used to probe the activity of orphan compounds using a so-called “target fishing” approach. Here, we present a proof of concept study using an in silico/in vitro target fishing approach on the fungal secondary metabolite atromentin. The procedure relies on a computational screening for activity identification coupled with experimental trials for dose-response characterization. Computational results identified estrogen receptors and 17-β-hydroxysteroid dehydrogenase as potential targets. Experiments confirmed a weak estrogenic activity, supporting the reliability of the procedure. Despite limited estrogenicity of atromentin, the proposed inhibition of 17-β-hydroxysteroid dehydrogenase should be considered as a source for endocrine disruptive effects.

Citation

Dellafiora, L., Aichinger, G., Geib, E., Sánchez-Barrionuevo, L., Brock, M., Cánovas, D., Dall'Asta, C., & Marko, D. (2019). Hybrid in silico/in vitro target fishing to assign function to “orphan” compounds of food origin: the case of the fungal metabolite atromentin. Food Chemistry, 270, 61-69. https://doi.org/10.1016/j.foodchem.2018.07.027

• Journal Article Type: Article
• Acceptance Date: Jul 2, 2018
• Online Publication Date: Jul 4, 2018
• Publication Date: Jan 1, 2019
• Deposit Date: Aug 13, 2018
• Publicly Available Date: Jul 5, 2019
• Journal: Food Chemistry
• Print ISSN: 0308-8146
• Electronic ISSN: 1873-7072
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 270
• Pages: 61-69
• DOI: https://doi.org/10.1016/j.foodchem.2018.07.027
• Keywords: Atromentin; Target fishing; Estrogenic activity; Fungal metabolite; Activity assignment; 17-β-Hydroxysteroid dehydrogenase
• Public URL: https://nottingham-repository.worktribe.com/output/1029080
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S030881461831166X?via%3Dihub#!
• Additional Information: This article is maintained by: Elsevier; Article Title: Hybrid in silico/in vitro target fishing to assign function to “orphan” compounds of food origin – The case of the fungal metabolite atromentin; Journal Title: Food Chemistry; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.foodchem.2018.07.027; Content Type: article; Copyright: © 2018 Elsevier Ltd. All rights reserved.
• Contract Date: Aug 14, 2018