Journal article
Processing of NMR and MS metabolomics data using chemometrics methods: a global tool for fungi biotransformation reactions monitoring.
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Palaric C
Plateforme-analytique, Institut de Chimie de Picardie FR CNRS 3085, Université de Picardie Jules Verne, 33 rue Saint Leu, 80039, Amiens, France.
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Pilard S
Plateforme-analytique, Institut de Chimie de Picardie FR CNRS 3085, Université de Picardie Jules Verne, 33 rue Saint Leu, 80039, Amiens, France. serge.pilard@u-picardie.fr.
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Fontaine JX
BIOPI EA 3900, Biologie des Plantes et Innovation, Université de Picardie Jules Verne, 1 rue des Louvels, 80000, Amiens, France.
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Boccard J
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211, Geneva 4, Switzerland.
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Mathiron D
Plateforme-analytique, Institut de Chimie de Picardie FR CNRS 3085, Université de Picardie Jules Verne, 33 rue Saint Leu, 80039, Amiens, France.
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Rigaud S
Plateforme-analytique, Institut de Chimie de Picardie FR CNRS 3085, Université de Picardie Jules Verne, 33 rue Saint Leu, 80039, Amiens, France.
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Cailleu D
Plateforme-analytique, Institut de Chimie de Picardie FR CNRS 3085, Université de Picardie Jules Verne, 33 rue Saint Leu, 80039, Amiens, France.
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Mesnard F
BIOPI EA 3900, Biologie des Plantes et Innovation, Université de Picardie Jules Verne, 1 rue des Louvels, 80000, Amiens, France.
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Gut Y
Technologie Servier, 27 rue Eugène Vignat, 45000, Orléans, France.
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Renaud T
Technologie Servier, 27 rue Eugène Vignat, 45000, Orléans, France.
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Petit A
Technologie Servier, 27 rue Eugène Vignat, 45000, Orléans, France.
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Beaumal JY
Technologie Servier, 27 rue Eugène Vignat, 45000, Orléans, France.
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Molinié R
BIOPI EA 3900, Biologie des Plantes et Innovation, Université de Picardie Jules Verne, 1 rue des Louvels, 80000, Amiens, France.
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Published in:
- Metabolomics : Official journal of the Metabolomic Society. - 2019
English
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.
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Language
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Open access status
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closed
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Identifiers
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Persistent URL
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https://sonar.ch/global/documents/271720
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