Generation of stilbene antimicrobials against multiresistant strains of Staphylococcus aureus through biotransformation by the enzymatic secretome of Botrytis cinerea

Article Article scientifique Article Generation of stilbene antimicrobials against multiresistant strains of Staphylococcus aureus through biotransformation by the enzymatic secretome of Botrytis cinerea eng 2020 author Righi Davide 816112 author Huber Robin 751322 author Koval Alexey 0000-0002-8920-4426 910996 author Marcourt Laurence 729234 author Schnee Sylvain author Le Floch Anaïs 870510 author Ducret Verena 596806 author Perozzo Remo 625237 author De Ruvo Concetta Carlotta 893780 author Lecoultre Nicole author Michellod Emilie author Ebrahimi Samad N. author Rivara-Minten Elisabeth 23985 author Katanaev Vladimir 0000-0002-7909-5617 910192 author Perron Karl 45679 author Wolfender Jean-Luc 135649 author Gindro Katia author Ferreira Queiroz Emerson 135675 2347-2356 10.1021/acs.jnatprod.0c00071 32705864 0163-3864 https://pubs.acs.org/doi/10.1021/acs.jnatprod.0c00071 The biotransformation of a mixture of resveratrol and pterostilbene was performed by the protein secretome of Botrytis cinerea. Several reaction conditions were tested to overcome solubility issues and to improve enzymatic activity. Using MeOH as cosolvent, a series of unusual methoxylated compounds was generated. The reaction was scaled-up, and the resulting mixture purified by semipreparative HPLC-PDA-ELSD-MS. Using this approach, 15 analogues were isolated in one step. Upon full characterization by NMR and HRMS analyses, eight of the compounds were new. The antibacterial activities of the isolated compounds were evaluated in vitro against the opportunistic pathogens Pseudomonas aeruginosa and Staphylococcus aureus. The selectivity index was calculated based on cytotoxic assays performed against human liver carcinoma cells (HepG2) and the human breast epithelial cell line (MCF10A). Some compounds revealed remarkable antibacterial activity against multidrug-resistant strains of S. aureus with moderate human cell line cytotoxicity. Biotransformation Fungal secretome Stilbenes HPLC-PDA-ELSD-MS Isolation Structural elucidation Multidrug-resistant strains S. aureus Dewey 580 Dewey 612 Swiss National Science Foundation Improving natural products chemical biodiversity for drug discovery by fungal secretome assisted biotransformation 205321_182438 CH Project funding Swiss National Science Foundation NMR 600MHz for metabolomics and biomarker identification for life sciences, chemical biology and medical projects at the University of Geneva 316030_164095 CH Infrastructure 45 Département des sciences végétales 163 134 Département de physiologie cellulaire et métabolisme 21C false 882 Phytochimie et produits naturels bioactifs 1264 Voies de signalisation oncogéniques 998 Journal of Natural Products 83 8 c979491f-1242-46c0-bb98-aceb064f6761 Article (Accepted version) Public RighiJNP2020.pdf 891339 application/pdf Restricted 2021-07-28 519c3763-0f8b-4b3c-81de-19b417a40b75 Article (Published version) Restricted Righi2020.pdf 1614816 application/pdf openAccess Faculté des sciences / Section de biologie / Département des sciences végétales Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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Generation of stilbene antimicrobials against multiresistant strains of Staphylococcus aureus through biotransformation by the enzymatic secretome of Botrytis cinerea	Journal of Natural Products			2020	365	565

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De Ruvo, Concetta Carlotta