Plant sesquiterpene lactones

Abstract

Sesquiterpene lactones (STLs) are a prominent group of plant secondary metabolites predominantly found in the Asteraceae family and have multiple ecological roles and medicinal applications. This review describes the evolutionary and ecological significance of STLs, highlighting their roles in plant defence mechanisms against herbivory and as phytotoxins, alongside their function as environmental signalling molecules. We also cover the substantial role of STLs in medicine and their mode of action in health and disease. We discuss the biosynthetic pathways and the various modifications that make STLs one of the most diverse groups of metabolites. Finally, we discuss methods for identifying and predicting STL biosynthesis pathways. This article is part of the theme issue 'The evolution of plant metabolism'.

Keywords: bioinformatics; biosynthesis; medicinal; plants; sesquiterpene; specialized metabolism.

Figure 1.

Types of sesquiterpene lactones (STL) in plants. Five major STL types (germacranolides, guaianolides, eudesmanolides, heliangolides and pseudoguaianolides), three minor STL types (elemanolides, eremophilanolides and xanthanolides) and artemisinin are represented by their structural backbones and specific examples, together with an example of a plant species where the molecule is found. References are: (1) Saussurea costus on way from Ghangria to Hemkund at Valley of Flowers National Park—during LGFC—VOF 2019 [5]. Image by Vinayaraj on https://www.commons.wikimedia.org, (2, 4) Pareek et al. 2011 [9], (3) Tanacetum parthenium—Botanischer Garten Mainz IMG 5501.JPG by Oceancetaceen on https://www.commons.wikimedia.org, (5, 7, 9, 10, 28) Cheikh et al. 2022 [10], (6) Michelia Champaca Malaysia.jpg by Tu7uh on https://www.commons.wikimedia.org, (8) Inula helenium L., 1753 by Thibault Lefort, 2018, Charente-Maritime on flickr.com, (11) photo by Mauricio Mercadante, cc-by-nc-sa available from eol.org/pages/5118025, Encyclopedia of Life, (12) Branquinho et al. 2020 [11], (13) photo by Alex Popovkin, Bahia, Brazil, cc-by-nc-sa available from https://eol.org/pages/47145431, (14) Alexandre Schefer et al. 2017 [12], (15) Arnica montana L., 1753 by Thibault Lefort, 2013, Hautes-Pyrénées on flickr.com, (16) Schmidt 2023 [13], (17) Parthenium hysterophorus OB−20130613-DSC_4736 by pennyjr cc by-nc-nd 2.0 on flickr.com, (18) Kaur et al. 2021 [14], 19) Z2A9137 Elephantopus scaber on flickr.com/photos/budak/, cc by-nc-nd 2.0, (20) Liang et al. 2008 [15], (21) Vernonia amygdalina by forestowlet available on https://www.commons.wikimedia.org, (22) Kimani et al. 2017 [16], (23) Parasenecio tschonoskii by Qwert1234 available on https://www.commons.wikimedia.org, (24) Liu et al., 2020 [17], (25) Xanthium strumarium habit Campo de Calatrava, Spain by Javier Martin available on https://www.commons.wikimedia.org/, (26) Zhang et al., 2022 [18], (27) Artemisia annua by Jorge Ferreira available on https://www.commons.wikimedia.org.

Figure 2.

Biosynthetic pathways of STLs. The major subclasses of STLs with their ring structures coloured as indicated: germacranolides (grey), heliangolides (purple), guaianolides (pink), pseudoguaianolides (cyan), eudesmanolides (green) and artemisinin (red). Compounds that are outlined in red (costunolide, parthenolide and micheliolide) are major examples of the modifications of STL subclasses from germacranolide (grey) to guaianolide (pink). Artemisinin, as a unique STL, is coloured in red. The abbreviations are as follows: 1-deoxy-d-xylulose 5-phosphate (DXP); 2-C-methyl-D-erythritol 4-phosphate (MEP); 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA); acetyl-coenzyme A (acetyl-CoA); alcohol dehydrogenase 1 (ADH1); aldehyde dehydrogenase 1 (ALDH1); amorpha-4,11-diene (AD); amorpha-4,11-diene synthase (ADS); amorphadiene oxidase (AMO, CYP71AV1); artemisinic aldehyde double-bond reductase (DBR2); cytochrome P450 monooxygenase (CYP); cytochrome P450 reductase (CPR); dimethylallyl diphosphate (DMAPP); farnesyl diphosphate (FPP); geranylgeranyl diphosphate (GGPP); germacrene A (GA); germacrene A oxidase (GAO); germacrene A synthase (GAS); isopentenyl diphosphate (IPP); isopentenyl diphosphate isomerase (IDI); mevalonate (MVA), mevalonate diphosphate (MVAPP).

Figure 3.

Examples of modifications of STLs. (a) The chlorinated guaianolide chlorohyssopifolin A, (b) the acetoxylated germacranolide pyrethrosin, and (c) the glucosylated germacranolide 15-O-β-D-glucopyranosyl-11β,13-dihydrourospermal A.

Figure 4.

Cluster map of sesquiterpene synthases in 94 species. Sesquiterpene types are indicated in rows and species in columns, while the cell colours represent the number of given synthases in a species.