A century of studying plant secondary metabolism-From "what?" to "where, how, and why?"

Abstract

Over the past century, early advances in understanding the identity of the chemicals that collectively form a living plant have led scientists to deeper investigations exploring where these molecules localize, how they are made, and why they are synthesized in the first place. Many small molecules are specific to the plant kingdom and have been termed plant secondary metabolites, despite the fact that they can play primary and essential roles in plant structure, development, and response to the environment. The past 100 yr have witnessed elucidation of the structure, function, localization, and biosynthesis of selected plant secondary metabolites. Nevertheless, many mysteries remain about the vast diversity of chemicals produced by plants and their roles in plant biology. From early work characterizing unpurified plant extracts, to modern integration of 'omics technology to discover genes in metabolite biosynthesis and perception, research in plant (bio)chemistry has produced knowledge with substantial benefits for society, including human medicine and agricultural biotechnology. Here, we review the history of this work and offer suggestions for future areas of exploration. We also highlight some of the recently developed technologies that are leading to ongoing research advances.

Figure 1.

Structures of a selection of plant secondary metabolites, showing their biosynthetic origins, in planta functions, and uses or importance in plant biology. The bracket under each compound indicates the in planta function (green letter referring to a green box) and potential use or area of biology that the study of the compound has impacted (blue letter referring to a blue box). Arrows link precursors from primary metabolism (central circle) to the end products. Salicylic acid can be derived from phenylalanine or isochorismate (shikimate pathway intermediate).

Figure 2.

Historical timeline for research on lignin, lignans, flavonoids, and alkaloids, with a focus on phenolic pathways. ANR, anthocyanidin reductase; CHI, chalcone isomerase; CHS, chalcone synthase; F5H, ferulate:coniferaldehyde 5-hydroxylase; IF, isoflavonoid; IFS, isoflavone synthase; LAR, leucoanthocyanidin reductase; PA, proanthocyanidin (condensed tannin); PAL, L-phenylalanine ammonia-lyase; SS, strictosidine synthase; TAL, L-tyrosine ammonia-lyase. The enzymes are referenced further in the text.

Figure 3.

Timeline for the development of techniques that have driven research on plant secondary metabolites. Pictures are from: MS imaging (Zhang et al. 2023); FRET (Herud-Sikimić et al. 2021); mutant analysis (Adiji et al. 2021); synthetic biology (Brophy et al. 2022); and single-cell transcriptomics (Nolan et al. 2023). The picture bottom left is a vintage lithograph showing the white willow, Salix alba (original book source: Prof. Dr Otto Wilhelm Thomé, Flora von Deutschland, Österreich und der Schweiz 1885, Gera (Germany)—public domain, https://commons.wikimedia.org/w/index.php?curid=2358667). The figure from Brophy et al. (2022) is reprinted with permission from AAAS. Other images are our own or licensed under a Creative Commons Attribution License (CC BY, https://creativecommons.org/licenses/by/4.0/) by Zhang et al. (2023), Herud-Sikimić et al. (2021), and Nolan et al. (2023). EST, expressed sequence tag; FLIM, fluorescence lifetime imaging microscopy.

Figure 4.

Examples of techniques used to visualize the localization of secondary metabolites. Each technology shown here is designed to image abscisic acid (ABA). A) A genetically encoded reporter (Wu et al. 2018); B) a FRET sensor (Rowe et al. 2023); C) a fluorogenic, small molecule-based probe (Yang et al. 2022), and this image was reprinted with permission from Yang et al. (2022) copyright 2022 American Chemical Society; and D) an MALDI MS imaging method for imaging phytohormones cytokinin (CK) and ABA (Shiono et al. 2017), and this image was reprinted with permission from Shiono et al. (2017), copyright 2017 American Chemical Society. Images are licensed under a Creative Commons Attribution License (CC BY, https://creativecommons.org/licenses/by/4.0/) by Wu et al. (2018) and Rowe et al. (2023).