Biocatalytic regioselective O-acylation of sesquiterpene lactones from chicory: a pathway to novel ester derivatives

• Published in: ChemBioChem
• Main Authors: Mosheim, Juan Rodriguez, Ruggieri, Francesca, Humeau, Catherine, Hance, Philippe, Willand, Nicolas, Hilbert, Jean-Louis, Heuson, Egon, Froidevaux, Rénato
• Other Authors: BioEcoAgro - Equipe 6 - Biotransformation / Enzymes and Biocatalysis, BioEcoAgro - UMR transfrontalière INRAe - UMRT1158, 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 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), Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177 (M2SV), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Laboratoire Réactions et Génie des Procédés (LRGP), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), BioEcoAgro - Equipe 5 - Specialized Metabolites of Plant Origin, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Centrale Lille-Institut de Chimie - CNRS Chimie (INC-CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), CPER BIHautEcodeFrance, Region Hauts-de-France, Doctoral schools 104 SMRE and 446 BSL
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2024
• Subjects: Lipase; CAL-B; Sesquiterpene Lactone; Biocatalytic Acylation; Chicory Root; [CHIM]Chemical Sciences; [CHIM.CATA]Chemical Sciences/Catalysis; [INFO.INFO-BT]Computer Science [cs]/Biotechnology; Antarc*; Antarctica
• Online Access: https://hal.science/hal-04403169; https://hal.science/hal-04403169/document; https://hal.science/hal-04403169/file/ChemBioChem_Mosheim_manuscript.pdf; https://doi.org/10.1002/cbic.202300722

International audience We report the first biocatalytic modification of sesquiterpene lactones (STLs) found in the chicory plants, specifically lactucin (Lc), 11β,13dihydrolactucin (DHLc), lactucopicrin (Lp), and 11β,13-dihydrolactucopicrin (DHLp). The selective O-acylation of their primary alcohol group was carried out by the lipase B from Candida antarctica (CAL-B) using various aliphatic vinyl esters as acyl donors. Perillyl alcohol, a simpler monoterpenoid, served as a model to set up the desired O-acetylation reaction by comparing the use of acetic acid and vinyl acetate as acyl donors. Similar conditions were then applied to DHLc, where five novel ester chains were selectively introduced onto the primary alcohol group, with conversions going from >99 % (acetate and propionate) to 69 % (octanoate). The synthesis of the corresponding O-acetyl esters of Lc, Lp, and DHLp was also successfully achieved with near-quantitative conversion. Molecular docking simulations were then performed to elucidate the preferred enzyme-substrate binding modes in the acylation reactions with STLs, as well as to understand their interactions with crucial amino acid residues at the active site. Our methodology enables the selective O-acylation of the primary alcohol group in four different STLs, offering possibilities for synthesizing novel derivatives with significant potential applications in pharmaceuticals or as biocontrol agents. Nous rapportons la première modification biocatalytique de lactones sesquiterpéniques (STL) présentes dans la chicorée, à savoir la lactucine (Lc), la 11β,13dihydrolactucine (DHLc), la lactucopicrine (Lp) et la 11β,13-dihydrolactopicrine (DHLp). La lipase B de Candida antarctica (CAL-B) a procédé à la O-acylation sélective de leur groupe alcool primaire en utilisant divers esters vinyliques aliphatiques comme donneurs d'acyle. L'alcool périllylique, un monoterpénoïde plus simple, a servi de modèle pour mettre en place la réaction d'O-acétylation souhaitée en comparant l'utilisation de l'acide ...