Terpenes are the most abundant and diverse family of natural compounds, with over 64,000 structures identified to date. Their significance to humanity is undeniable, with plants rich in terpenes having been employed for medicinal purposes across the globe. Thanks to technological advances, numerous terpenes and terpenoid compounds have been thoroughly examined and are now acknowledged for their promising biological activities, such as antimicrobial, anti-inflammatory, and antitumor properties. Industrial chicory (Cichorium intybus var. sativum) is a biennial plant of the Asteraceae family and the genus Cichorium, native to the Mediterranean region and the north of Africa. The history of this plant use as a herbal remedy dates back to the ancient Greeks, Egyptians and Chinese, who employed it to treat various respiratory, hepatobiliary and digestive pathologies. Nowadays it is primarily cultivated in Belgium, the Netherlands and in the north of France. In modern history, the root of industrial chicory has been used in the food sector, particularly as a substitute for coffee. However, since the mid-1980s, it has primarily been exploited for its inulin content (up to 70 % of its dry mass). Inulin can also be hydrolyzed and used in the production of fructose and oligofructose. The fresh roots from industrial chicory (Cichorium Intybus var. sativum) typically contain around 3 % of secondary metabolites by weight. Such compounds are mainly phenolic and polyphenolic compounds, sesquiterpene lactones (STLs) and flavonoids (to a lesser extent). For the purposes of this work, we focused on the sesquiterpene lactones found in the root of industrial chicory. Around fifteen STLs belonging to the guaianolide sub-family have been identified, with lactucin (Lc) and its ester analog lactucopicrin (Lp) being the most well-known, as they were previously identified in wild lettuce (Lactuca virosa). Within the root of industrial chicory, these STLs predominantly exist as conjugated oxalate and glucoside derivatives. The previous STLs, along with their respective saturated analogs, 11β,13-dihydrolactucin and 11β,13-dihydrolactucopicrin, can also be found in the root. The structural characteristics of the main STLs from chicory have been described in detail in the literature (Figure .). Sesquiterpene lactones are typically highly functionalized terpenes, conceived by nature in part as plant defense tools to cope with environmental stresses. Indeed, many of them also possess pharmacological properties. These terpenes are known for their antitumor and anti-inflammatory activities, with over 1,500 scientific publications between 1990 and 2010 focusing on these two properties. Sesquiterpene lactones are also reported for their antimalarial, antioxidant, and antimicrobial properties. Regarding STLs derived from chicory, several of them have demonstrated interesting antimicrobial properties. Both 11β, 13dihydrolactucin (DHLc) and lactucopicrin (DHLp) effectively inhibited the growth of Pseudomonas aeruginosa, DHLp was also effective against Staphylococcus aureus, while DHLc showed good results against different strains of Candida. Antiparasitic properties were reported for STLs from chicory such as lactucin and lactucopicrin, notably against Plasmodium falciparum strain Honduras-1. Moreover, lactucin has also been linked to both in vivo and in vitro anti-adipogenesis effects and anticancer activities. Figure . Guiaianolide skeleton and structure, log (P) and surface polarity of the main non-conjugated STLs found in chicory root. Structure-activity relationship studies have shown that the main structural features responsible for most of the biological activities of STLs are the presence of a α-methylene-gamma lactone (α-MGL) and an unsaturated cyclopentenone moieties. These electrophilic moieties can interact with cysteine and other amino acid residues of certain proteins, notably via Michael addition reactions. While those have been identified as the main pharmacophores, there are other factors that play a role in modulating reactivity, such as lipophilicity, the number of alkylating sites (e.g. Michael acceptors, primary halogens) and the presence of certain ester side chains. While the synthesis of new STL esters hasn't been explored thoroughly yet, a few examples in the literature have shown interesting results. Kitai et al. recently carried out the synthesis of several ester derivatives (propyl, butyl, pentyl and 2-methoxy ethynyl) of the STL sonchifolinic acid, isolated from Yacon (Smallanthus sonchifolius), and studied their cytotoxicity by evaluating the influence of these side chains. It was observed that the introduction of alkyl chains of increasing length significantly enhanced the cytotoxicity of the parent molecule, and that this effect was probably due to a higher lipophilicity. A similar effect was shown for the STL helenalin, where its acetate and isobutyrate ester derivatives showed a higher toxicity towards tumor cells. The difference in cytotoxicity was shown to be directly related to both the size and the lipophilicity of the side chain. However, beyond a certain point, the steric effects of the alkyl chain may impede the accessibility of the molecule's pharmacophore (e.g., the α-MGL group and/or the cyclopentenone moiety) and cause a decrease in activity. Moreover, a recent paper by Zhang et al. describes the synthesis of several semi-synthetic ester derivatives of the STL scabertopin (isolated from Elephantopus scaber). These esters were produced by introducing several side chains containing aromatic moieties, and their evaluation as potential anti-cancer agents for non-small cell lung cancer also showed promising results. The possibility to generate new derivatives from these compounds for pharmaceutical and agri-food industries applications is a promising avenue of research. The present work explores and establishes enzymatic methods for the functionalization of terpenoids previously extracted from chicory root. In this initial study, we focused specifically on the synthesis of ester analogues. Sesquiterpene lactones frequently possess multiple hydroxyl functions, allowing the grafting of various groups such as alkyl chains. By proceeding in this manner, we can modulate their hydrophilicity, and in turn, their biological properties, including their ability to interact with plasma membranes and to cross biological barriers.