Processing of NMR and MS metabolomics data using chemometrics methods: a global tool for fungi biotransformation reactions monitoring
| Autor: | Roland Molinié, François Mesnard, Alain Petit, Cécile Palaric, Serge Pilard, Yoann Gut, Julien Boccard, Dominique Cailleu, Jean-Yves Beaumal, Tristan Renaud, Sébastien Rigaud, Jean-Xavier Fontaine, David Mathiron |
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| Přispěvatelé: | Plateforme Analytique (PFA), Université de Picardie Jules Verne (UPJV), Biologie des Plantes et Innovation - UR UPJV 3900 (BIOPI), Université de Picardie Jules Verne (UPJV)-Transfrontalière BioEcoAgro - UMR 1158 (BioEcoAgro), Université d'Artois (UA)-Université de Liège-Université de Picardie Jules Verne (UPJV)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Université d'Artois (UA)-Université de Liège-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Magnetic Resonance Spectroscopy
Filamentous fungi Endocrinology Diabetes and Metabolism Clinical Biochemistry Human metabolism 01 natural sciences Biochemistry Mass Spectrometry Chemometrics 03 medical and health sciences Biotransformation [CHIM]Chemical Sciences Humans Metabolomics Analytical strategy 030304 developmental biology 2. Zero hunger Principal Component Analysis 0303 health sciences ddc:615 Molecular Structure Drug discovery Chemistry 010401 analytical chemistry Fungi UHPLC–UV–MS NMR 0104 chemical sciences Metabolomics data Biochemical engineering Consensus-OPLS-DA Histamine H3 Antagonists |
| Zdroj: | Metabolomics, Vol. 15, No 8 (2019) Metabolomics Metabolomics, Springer Verlag, 2019, 15 (8), ⟨10.1007/s11306-019-1567-5⟩ Metabolomics, 2019, 15 (8), ⟨10.1007/s11306-019-1567-5⟩ |
| ISSN: | 1573-3882 1573-3890 |
| DOI: | 10.1007/s11306-019-1567-5⟩ |
| Popis: | Introduction Biotransformation constitutes an important aspect of the drug discovery process, to mimic human metabolism of active principal ingredient but also to generate new chemical entities. Several microorganisms such as fungi are well adapted to transform drug, whether at the stage of screening or for large-scale production. Objectives Due to the high chemical complexity of the biotransformation media, it seems attractive to develop new analytical strategies in order to guarantee an adequate monitoring and optimize the production of targeted metabolites or drug candidates. Methods The model designed for this purpose concerns the biotransformation of a potential histamine H3 antagonist (S38093) in order to produce phase I metabolites. MS, NMR and chemometrics tools were used to monitor biotransformation reactions. Results First, a screening of eleven filamentous fungi was carried out by UHPLC–UV–MS and principal component analysis to select the best candidates. Subsequently, MS (tR, m/z) and NMR (1H, JRES) fingerprints associated with Consensus OPLS-DA multiblock approach were used to better understand the bioreaction mechanisms in terms of nutrient consumption and hydroxylated metabolites production. Then an experimental design was set up to optimize the production conditions (pH, kinetic) of these target metabolites. Conclusion This study demonstrates how NMR and MS acquisitions combined with chemometric methods offer an innovative analytical strategy to have a grasp of functionalization mechanisms, and identify metabolites and other compounds (amino acids, nutrients, etc.) in complex biotransformation mixtures. |
| Databáze: | OpenAIRE |
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