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

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 id...

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Main Authors: Dellafiora, Luca, Aichinger, Georg, Geib, Elena, Sánchez-Barrionuevo, Leyre, Brock, Matthias, Cánovas, David, Dall'Asta, Chiara, Marko, Doris
Format: Article
Language:English
Published: Elsevier 2019
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Online Access:https://eprints.nottingham.ac.uk/53975/
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author Dellafiora, Luca
Aichinger, Georg
Geib, Elena
Sánchez-Barrionuevo, Leyre
Brock, Matthias
Cánovas, David
Dall'Asta, Chiara
Marko, Doris
author_facet Dellafiora, Luca
Aichinger, Georg
Geib, Elena
Sánchez-Barrionuevo, Leyre
Brock, Matthias
Cánovas, David
Dall'Asta, Chiara
Marko, Doris
author_sort Dellafiora, Luca
building Nottingham Research Data Repository
collection Online Access
description 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.
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publishDate 2019
publisher Elsevier
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spelling nottingham-539752019-07-04T04:30:27Z https://eprints.nottingham.ac.uk/53975/ 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 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. Elsevier 2019-01-01 Article PeerReviewed application/pdf en cc_by_nc_nd https://eprints.nottingham.ac.uk/53975/1/Manuscript_Revision_Target%20fishing_complete.pdf Dellafiora, Luca, Aichinger, Georg, Geib, Elena, Sánchez-Barrionuevo, Leyre, Brock, Matthias, Cánovas, David, Dall'Asta, Chiara and Marko, Doris (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 . pp. 61-69. ISSN 0308-8146 Atromentin; Target fishing; Estrogenic activity; Fungal metabolite; Activity assignment; 17-β-Hydroxysteroid dehydrogenase https://www.sciencedirect.com/science/article/pii/S030881461831166X?via%3Dihub doi:10.1016/j.foodchem.2018.07.027 doi:10.1016/j.foodchem.2018.07.027
spellingShingle Atromentin; Target fishing; Estrogenic activity; Fungal metabolite; Activity assignment; 17-β-Hydroxysteroid dehydrogenase
Dellafiora, Luca
Aichinger, Georg
Geib, Elena
Sánchez-Barrionuevo, Leyre
Brock, Matthias
Cánovas, David
Dall'Asta, Chiara
Marko, Doris
Hybrid in silico/in vitro target fishing to assign function to “orphan” compounds of food origin – The case of the fungal metabolite atromentin
title Hybrid in silico/in vitro target fishing to assign function to “orphan” compounds of food origin – The case of the fungal metabolite atromentin
title_full Hybrid in silico/in vitro target fishing to assign function to “orphan” compounds of food origin – The case of the fungal metabolite atromentin
title_fullStr Hybrid in silico/in vitro target fishing to assign function to “orphan” compounds of food origin – The case of the fungal metabolite atromentin
title_full_unstemmed Hybrid in silico/in vitro target fishing to assign function to “orphan” compounds of food origin – The case of the fungal metabolite atromentin
title_short Hybrid in silico/in vitro target fishing to assign function to “orphan” compounds of food origin – The case of the fungal metabolite atromentin
title_sort hybrid in silico/in vitro target fishing to assign function to “orphan” compounds of food origin – the case of the fungal metabolite atromentin
topic Atromentin; Target fishing; Estrogenic activity; Fungal metabolite; Activity assignment; 17-β-Hydroxysteroid dehydrogenase
url https://eprints.nottingham.ac.uk/53975/
https://eprints.nottingham.ac.uk/53975/
https://eprints.nottingham.ac.uk/53975/