Plant natural products, the subset of metabolic intermediates made by plants which humans utilize in medicine and industry, are of increasing importance, with some 40% of medicines being plant-derived. While their applications have been appreciated since antiquity, they are often taxonomically restricted, a fact that has, until recently, posed a major hurdle to understanding their biosynthesis and to their bioengineering. That said, recent 21st-century tools, such as genome editing, transcript co-expression analysis, single-cell biology, and non-targeted metabolomics, are transforming our ability both to understand the biosynthesis of these compounds and to better assess their bioactivities, and are beginning to enable more sustainable production in heterologous systems. In the following special issue, we present: one commentary, three brief communications, eight reviews, and 12 research articles that reflect the current state of the art in plant natural product research. Salicylic acid is a natural phenolic compound initially identified in willow bark and used by humans for more than 200 years for its anti-inflammatory and analgesic properties, before more recently emerging as a vital plant defense hormone. In their commentary, Li and Luo (2026) review a trio of independent papers published last year (Liu et al., 2025; Wang et al., 2025; Zhu et al., 2025), revealing the full identity of the phenylalanine pathway of salicylic acid that operates as an alternative to the chorismate pathway. These studies collectively adopted high-throughput genetic screening strategies and co-expression analysis of a conserved phenylalanine lyase (PAL)-dependent pathway, originating with the conversion of phenylalanine to trans-cinnamic acid by PAL, followed by its subsequent conversion to benzoyl CoA catalyzed via the three enzymes cinnamate: CoA ligase, cinnamoyl CoA hydratase/ dehydrogenase, and 3-ketoacyl CoA thiolase in series. Benzoyl CoA is next conjugated with benzyl alcohol, forming benzyl butanoate, which is subsequently converted to benzyl salicylate before being hydrolyzed to salicylic acid. This commentary nicely delineates modern approaches toward pathway discovery, which have also recently been adopted for a range of other natural products, including paclitaxel, mecaline, vinblastine, tropane alkaloids, and many more (Caputi et al., 2018; Chavez et al., 2022; Zhang et al., 2023; Qin et al., 2025). The Brief Communications here cover three of the most powerful recent approaches in plant natural product biology, namely genome sequencing, genome editing, and metabolomics. In their paper, Wang et al. describe the chromosome-scale genome of the medicinal plant Dioscorea nipponica, which is a rich source of diosgenin-type precursors for the steroidal drug industry, revealing a cluster of nine out of 11 26-O-β-glucosidases whose expression mirrors the tissue-specific expression of the steroidal saponins (Wang et al., 2026c). Wang et al. further provided kinetic characterization of several of these enzymes, revealing considerable functional redundancy in 3-O-glycosylation, which is discussed in terms of convergent evolution. CRISPR and related forms of gene editing have revolutionized biology (see (Li et al., 2025) and (Yaşar et al., 2026) for reviews), and despite a short time lag for optimizing this system for medicinal plants, this is also the case for medicinal plants. In their communication, Yao et al. report the engineering of prime editors for Salvia miltorrhiza (Yao et al., 2026). While CRISPR/Cas9-mediated gene knockout has been reported for this species (Cao et al., 2024), precise genome editing has to date proven challenging in this important traditional Chinese medicinal herb. Here, Yao et al. developed an optimized prime editing system via promoter engineering, pegRNA structural refinement, and DNA mismatch repair pathway suppression, establishing a platform for metabolic engineering of Salvia bioactive compounds. In the final brief communication of this special issue, Deng et al. describe how the metabolic profiling of lactifers in rubber trees provides an important baseline understanding of the metabolism of lactifers in the rubber tree (Deng et al., 2026). In their study population, metabolome analysis was carried out across 72 cultivars and 82 wild rubber germplasms, highlighting an upregulation of amino acids and nucleic acids and their derivatives, but a decline in the levels of secondary metabolites on domestication, with the exception of a clear increase in isoprenoid metabolism. As such, this study provides further support to the theory that domestication of the metabolome of various crops tends to be species-specific (Alseekh et al., 2021). Two of the eight reviews in this collection cover medicinal plants in general. In their article, Chen et al. analyse advances, challenges, and prospects of genome editing of medicinal plants (Chen et al., 2026a). They explain that medicinal plants often only produce low levels of effective ingredients, produce relatively little biomass, and are often difficult to cultivate. Following this, they posit genome editing as holding great promise for agronomic and metabolic engineering-based pharmaceutical production. In doing so, they review the state of the art in gene editing in medicinal plants, covering both recent successes (see, for example, Li et al., 2021) and current limitations, and focusing on novel technologies to enhance regeneration rates of transgenic plants and AI-assisted approaches for predicting editing efficiency. They finish by describing the prospects of gene editing in the metabolic engineering of medicinal plants. The article by Fu et al. (2026) also reviews medicinal plants but from the perspective of specialized structures such as glandular trichomes, roots, rhizomes, lactifers, and heartwood (Fu et al., 2026). It describes how the form and function of such structures are under genetic, hormonal, and environmental control, as well as highlights how technological advances have provided new insights into this process and the perspectives for precision breeding and metabolic engineering that these insights provide. Three of the other six review papers concern specific areas of metabolism. First, Zhang et al. review the diversity, catalytic activities, mechanisms of plant prenyltransferases, and the heterologous production of prenylated natural products (Zhang et al., 2026f). These enzymes catalyze the transfer of C5 isoprenyl units to specific receptor molecules, including terpene precursors and aromatic compounds. Zhang et al. highlight how advances in synthetic biology and plant genomics have accelerated research also in this field, providing an exhaustive summary of more than 160 reported plant ubiquinone biosynthesis gene A-type prenyltransferases and select isopentyl diphosphate synthases, establishing a sound basis for prenylated natural products-based drug development. Secondly, Tan and Men provide an overview of the unprecedented diversity of sterols harbored by the plant kingdom, which, unlike animals and fungi that predominantly utilize cholesterol and ergosterol, produce over 250 diverse compounds, including β-sitosterol, stigmasterol, and campesterol, as well as sterol esters and steryl glycosides (Tan and Men, 2026). Their review not only describes the occurrence of these molecules but also their biosynthesis, transport, and functions, including those as membrane modulators. Tan and Men conclude by highlighting critical knowledge gaps that need to be addressed in order to comprehensively understand the potential of this class of phytochemicals. Sticking with sterols, the review by Chen et al. provided a very detailed mini-review focusing purely on tomato steroidal glycoalkaloids (Chen et al., 2026b). In their article, they describe the roles of these compounds in resistance to herbivores, pathogens, and environmental stress alongside their antifungal, antibacterial, and anticancer bioactivities, focusing on the immense improvements in our understanding of the underlying biosynthetic pathways and their regulators, which have been made in the last 15 years. The authors conclude by providing a perspective for future metabolic engineering approaches targeting this pathway. Zhang et al. provide a review of 100 years of research into tocopherol (vitamin E), highlighting advances in understanding its chemical composition, antioxidant potential, biosynthetic pathways, and the novel possible metabolic engineering strategies opened by the discovery of the seed-specific esterase, VTE7 (Zhang et al., 2026d). They also provide a forward-looking perspective encompassing the intelligent evolution of catalytic enzymes, the elucidation of precursor transport across membranes, and a deeper understanding of rare vitamins such as tocomonoerols. Scossa et al. review the use of convergence and parallelism as terms for evolutionary biology to define the occurrence of similar phenotypes with different evolutionary lineages that cannot be easily linked to descent from a shared ancestor (Scossa et al., 2026). They present cases of convergence during plant domestication, focusing on specialized metabolism, with the aim of understanding the intricacies of the natural selection, constraints, and drift underlying the recurrent appearance of complex traits. In the final review, Zhang et al. describe how the design principles of metabolons–multienzyme complexes, which enable substrate channeling, could be utilized as a means for programming metabolic fluxes as a way to better support plant natural product biosynthesis (Zhang et al., 2026a). They begin their review with a short overview of our current understanding of how metabolons work and detailing those in plants for which good functional evidence exists. Following that, they postulate how design rules for membrane anchoring, modular scaffolds, compartment targeting, and inducible control can be established while limitations, including metabolic burden, stochiometry, and leakiness, can be circumvented. They additionally outline how AI can create structurally aware generative models that can be optimized for enzymatic function, suggesting that metabolons represent a deployable technology for achieving higher titers of valuable natural products. In the first of 12 research papers in this collection, Zhang et al. provide near-complete genomes for four wild diploid raspberry species as well as the heterozygous diploid red raspberry and a closely related species (Zhang et al., 2026e). Pan-genome analysis highlighted expansions in flavonoid and terpenoid pathways while integrative transcriptome and metabolome analysis identified a glutathionine S-transferase gene as limiting anthocyanin pigmentation in R. ellipticus fruits. Collectively, the results presented here represent an excellent foundation for future improvement of this important berry species. This study is followed by two in tea. The first, that of Liu et al., revealed a novel acylated flavonoid, kaempferol-3-O-(6″-p-coumaroyl)-glucoside, whose accumulation correlated with cold stress severity (Liu et al., 2026c). Overexpression of the enzyme responsible for the synthesis of this compound in either Arabidopsis or tea, furthermore, resulted in elevated cold resistance, thereby validating the function of this metabolite. The second study, that of Jia et al., demonstrated that 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) was the causal gene underlying natural variation in adenosine and adenine content. Jia et al. further used phylogenetic analysis and protein structural modeling to reveal the occurrence of horizontal gene transfer events in the evolutionary history of plant MTANs (Jia et al., 2026). Three of the remaining research articles involve the characterization of gene modules. In the first of these, Liu et al. describe how the MdSEVEN IN ABSENTIA 1-MdWUSCHEL RELATED HOMEOBOX 8-MdELONGATED HYPOCOTYL 5 module links strigolactone and gibberellin signals via interaction with the respective strigolactone and gibberellin signaling repressors MdSMXL8 and MdRGL3a to regulate anthocyanin biosynthesis in apple (Liu et al., 2026a). In the second, Wang et al. identify that the GROWTH REGULATING FACTOR 20 (PagGRF20)–PagMYB4 regulatory module coordinates wood formation in poplar (Wang et al., 2026b), demonstrating that PagGRF20 overexpressing lines showed an approximate 20% increase in secondary xylem and 40% increase in cell wall thickness, while MYB4 interacts with PagGRF20 suppressing lignin biosynthesis genes, thereby potentially affecting the balance of cell wall components. Collectively, these results thus offer rich information for wood engineering. Finally, Liu et al. define how the Gastrodia elata AUXIN RESPONSE FACTOR-SWEET14 module balances secondary metabolite biosynthesis—namely that of gastrodin—to increase yield and quality in this important medicinal and edible plant (Liu et al., 2026b). These articles are followed by two more focused on more traditional biochemical-based approaches. The work of Zhang et al. revealed how phosphorylation fine-tunes ceramide synthase activity and stability, thereby modulating sphingolipid biosynthesis and immune responses (Zhang et al., 2026c). In their study, they discovered that LAG ONE HOMOLOG 2, the only long-chain ceramide synthase in Arabidopsis, is post-translationally regulated by casein kinase 2. They subsequently demonstrated that phosphorylation positively influences ceramide synthase activity and stability and that this provided resistance to the fungal toxin Fumonisin B1 and the bacterial pathogen Pseudomonas syringae. The article by Li et al. describes the biosynthesis of irregular terpenes, such as C11, C12, C16, and C17 terpenes, in Escherichia coli, which differ from the C5 polymers of plants (Li et al., 2026a). They subsequently demonstrate how screening C-methyltransferases by UniKP, they were able to synthesize methyl-isopentenyl pyrophosphate and subsequently polymerize it with C5 units to generate methyl β-elemene. As such, this study both expanded the chemical diversity of terpenoids and demonstrated the evolutionary plasticity of terpene synthases. Two further research papers focus on phenylpropanoids. That of Wang et al. focused on the characterization of philyrin, an antiviral lignan exclusive to Forsythia suspensa, which shows potent anti-influenza activity whose utility is hindered by low and variable natural accumulation (Wang et al., 2026d). There identification and deep characterization of important enzymes in the biosynthestic pathway elucidated the terminal steps of its production, thereby facilitating routes toward sustainable production of this pharmaceutical.Li et al. (2026b), meanwhile, identified UGT93 enzymes from Angelica decursiva as efficient biocatalysts for the glycosylation of bioactive prenylated phenolics like nodakenin. Enzymatic and structural analyses revealed a conserved substrate preference across the UGT93 family, driven by hydrophobic and aromatic residues in the binding pocket. The above findings highlight the significant potential of UGT93 enzymes for the metabolic engineering of plant-derived natural products. In their study, Wang et al. carried out a detailed analysis of the entire OMT gene family, firstly in tomato accessions, then across 20 major plant species, identifying a single ancestral lineage and thoroughly characterizing the evolution and specialization of this important gene family. They noted that among all COMT orthogroups, a single tandem duplicate cluster stands out as exclusively conserved and plays a distinct catalytic role. Moreover, ion mobility spectrometry showed that SlAOMT, a member of the CCoAOMT-like subfamily, catalyzes the methylation of luteolin to produce two isomeric products identified as diosmetin and chrysoeriol while losing the canonical catalytic function of the CCoAOMT subfamily. As such, their paper presents a useful blueprint for broad studies of the evolution of plant secondary metabolism (Wang et al., 2026a). The special issue is completed by the article of Zhang et al., who presented the development of a novel mass spectrometry imaging (MSI) platform, which could both expand the diversity of plant samples measured and the detection efficiency of plant metabolites (Zhang et al., 2026b). For this purpose, the platform, based on an Au nanoparticle-loaded MoS2 and doped graphene oxide flexible film substrate, combined with laser desorption/ionization-MSI, was established. This approach does not rely on sectioning and is matrix-free and demonstrated to offer high sensitivity for 10 classes of metabolites, overcoming several hurdles provided by plant tissues, including the fragility of leaves, water-richness of fruits, and high-lignin contents of roots. As such, it will likely prove a great boon for emerging strategies in pathway elucidation, which rely on high spatial resolution (see, for example, McClune et al., 2025). We sincerely believe that these articles represent a broad cross-section of current and prospective research in plant natural product biology, capturing both the technological advances and the burgeoning research being carried out in this highly exciting and rapidly moving field.
Fernie et al. (Mon,) studied this question.