Chemical profiling of bioactive secondary metabolites from the fungus Trichoderma reesei

To overcome challenges related to the energy area, IFP Energies nouvelles is now proposing a process to produce ethanol from lignocellulosic biomass. A cocktail of enzymes produced by the filamentous fungus Trichoderma reesei is used during the enzymatic hydrolysis step of this process. The genetic engineering of this fungus is one of the solutions that has allowed us to optimize the cost of this hydrolysis step in recent years. In the continuity of these studies, the question of the potential of secondary metabolites produced by this fungus must be asked today. IFPEN has a catalog of secretomes obtained from different deregulated strains and cultured under different conditions. These modifications could lead to the expression of silent genes and to the synthesis of undescribed secondary metabolites. The objective of this thesis is to propose an analytical methodology to obtain a chemical profiling of the complex mixtures of fungal secretomes available. Given the complexity of these mixtures, successive separative methods with high resolution mass spectrometry will have to be developed. Different types of separative methods using liquid chromatography, supercritical chromatography and ion mobility will be evaluated and compared. Bioinformatics tools and in particular the generation of molecular networks and statistical approaches will be implemented in order to exploit in a thorough, relevant and automated way the data resulting from the multidimensional analyses. New and efficient means of analytical characterization and data processing will be developed to advance in the molecular description of secretomes produced by Trichoderma reesei and thus contribute to the development of new products in the field of new energy technologies.

Keywords: Liquid chromatography, Supercritical fluid chromatography, Ion mobility, High resolution mass spectrometry, Metabolomics, Filamentous fungi, Bioinformatics, Epigenetics, Statistics, Chemometrics.

• Academic supervisor    Dr TOUBOUL David, CNRS, Institut de Chimie des Substances Naturelles (ICSN), Université Paris-Saclay, UPR 2301, 91198 Gif-sur-Yvette.
• Doctoral School    Chemical Sciences: Molecules, Materials, Instrumentation and Biosystems (2MIB) – Pairs-Saclay University (https://www.universite-paris-saclay.fr/en/doctoral-schools/chemical-sciences-molecules-materials-instrumentation-and-bio-systems)
• IFPEN supervisor    Dr LE MASLE Agnès, Pole Analyse Moléculaire, agnes.le-masle@ifpen.fr
• PhD location    IFPEN Lyon, France and ICSN Gif-sur-Yvette, France
• Duration and start date    3 years, starting in fourth quarter 2021
• Employer    IFPEN Lyon, France
• Academic requirements    University Master degree in analytical chemistry.
• Language requirements    Fluency in English
• Other requirements    Bioinformatics, strong interest in data treatment.