1. Screening for Biologically Annotated Drugs That Trigger Triacylglycerol Accumulation in the Diatom Phaeodactylum
- Author
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Khawla Seddiki, Eric Maréchal, Fabrice Rébeillé, Valérie Gros, Josselin Lupette, Melissa Conte, Caroline Barette, Coline Meï, Juliette Jouhet, Lina Juana Dolch, Physiologie cellulaire et végétale (LPCV), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Groupe Plateforme et Moyens Scientifiques et techniques communs / Centre de Criblage pour Molécules Bio-Actives (GPMS / CMBA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Genetics and Chemogenomics (GenChem), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Agence Nationale de la Recherche (DiaDomOil), Commissariat a l'Energie Atomique, Agence Nationale de la Recherche Programme Investissement d'Avenir (Oceanomics), and Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)
- Subjects
0301 basic medicine ,Active molecule screening ,Physiology ,Estrone ,Membrane lipids ,Phenotypic screening ,Drug Evaluation, Preclinical ,Plant Science ,Ethinyl Estradiol ,Phaeodactylum tricornutum ,03 medical and health sciences ,chemistry.chemical_compound ,Biosynthesis ,Biofuel ,Genetics ,Microalgae ,Ethylnylestradiol ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Lipids production ,Triglycerides ,chemistry.chemical_classification ,Diatoms ,Biological Products ,Triacylglycerol accumulation ,biology ,Dose-Response Relationship, Drug ,Catabolism ,Fatty acid ,Cytochrome P450 ,Glycerolipids ,Diatom ,Articles ,Feedstock ,biology.organism_classification ,Estrogen ,Sterol metabolism ,3. Good health ,030104 developmental biology ,chemistry ,Biochemistry ,Gene Expression Regulation ,Metabolic pathway ,biology.protein ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,Polyunsaturated fatty acid - Abstract
International audience; Microalgae are a promising feedstock for the production of triacylglycerol (TAG) for a variety of potential applications, ranging from food and human health to biofuels and green chemistry. However, obtaining high TAG yields is challenging. A phenotypic assay for the accumulation of oil droplets was developed to screen a library of 1,200 drugs, annotated with pharmacology information, to select compounds that trigger TAG accumulation in the diatom Phaeodactylum tricornutum Using this screen, we identified 34 molecules acting in a dose-dependent manner. Previously characterized targets of these compounds include cell division and cell signaling effectors, membrane receptors and transporters, and sterol metabolism. Among the five compounds possibly acting on sterol metabolism, we focused our study on ethynylestradiol, a synthetic form of estrogen that is used in contraceptive pills and known for its ecological impact as an endocrine disruptor. Ethynylestradiol impaired the production of very-long-chain polyunsaturated fatty acids, destabilized the galactolipid versus phospholipid balance, and triggered the recycling of fatty acids from membrane lipids to TAG. The P. tricornutum transcriptomic response to treatment with ethynylestradiol was consistent with the reallocation of carbon from sterols to acetyl-coenzyme A and TAG. The mode of action and catabolism of ethynylestradiol are unknown but might involve several up-regulated cytochrome P450 proteins. A fatty acid elongase, Δ6-ELO-B1, might be involved in the impairment of very-long-chain polyunsaturated fatty acids and fatty acid turnover. This phenotypic screen opens new perspectives for the exploration of novel bioactive molecules, potential target genes, and pathways controlling TAG biosynthesis. It also unraveled the sensitivity of diatoms to endocrine disruptors, highlighting an impact of anthropogenic pollution on phytoplankton.
- Published
- 2018
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