This and following posts will be serialized from a longer piece of writing. The focus will be broken up into sections:
· Secondary Metabolites as System Equilibrium
· Carbon Allocation Governs Chemical Expression
Signal Convergence and Wild Ecosystems
Phytochemical Ratios Emerge as Terroir
Signal Convergence
This model for plant secondary metabolism is shaped within a system defined by exudate-mediated microbial selection constrained by carbon allocation. The system produces many interacting signals that converge on a smaller set of regulatory pathways, where external conditions influence how metabolic activity is distributed across biosynthetic pathways. Secondary metabolite profiles emerge from the state of these nodes.
The hormone system acts as a convergence point where multiple upstream signals are integrated. Jasmonate and salicylate signaling pathways function as central regulatory nodes integrating microbial inputs with plant defense and metabolic responses (Pieterse et al., 2012). Microbial signals are perceived through plasma membrane–localized receptor-like kinases, including LysM-type receptors that recognize lipochitooligosaccharides (LCOs) and chitin-derived molecules produced by rhizobia and mycorrhizal fungi, as well as pattern recognition receptors that detect conserved microbial-associated signals. These receptor-mediated LCO pathways activate the common symbiosis signaling pathway (CSSP), including nuclear calcium oscillations and downstream transcriptional responses (Maillet et al., 2011; Oldroyd, 2013).
There appears to be substantial overlap between microbial perception pathways and hormone-regulated transcriptional networks, although the downstream metabolic consequences remain best resolved in selected systems rather than universally across plants (Maillet et al., 2011; Pieterse et al., 2012; Wang et al., 2018). As noted, signaling cascade intersects with hormone pathways, including jasmonate and salicylate networks, providing a route through which microbial recognition is coupled to broader regulatory systems that influence plant metabolism. Experimental evidence indicates that activation of symbiotic signaling pathways is associated with changes in expression of genes involved in secondary metabolism, linking microbial signal perception to downstream biosynthetic activity (Luginbuehl et al., 2017; Wang et al., 2018).
A more controlled demonstration of this relationship is observed in Artemisia annua, where inoculation with mycorrhizal fungi has been shown to increase artemisinin accumulation alongside upregulation of key biosynthetic genes, including ADS, CYP71AV1, DBR2, and ALDH1, with associated involvement of jasmonate signaling pathways (Mandal et al., 2015; Zhang et al., 2020). In this system, microbial association alters host regulatory pathways rather than contributing metabolites directly, resulting in coordinated changes in transcriptional activity and downstream metabolite production. The linkage between symbiont presence, hormone-mediated signaling, and activation of biosynthetic gene networks provides a mechanistic example of how closely associated microbial partners can modulate pathway flux and final chemical output.
Predictable regulatory and metabolic shifts have been demonstrated more directly in synthetic community studies, where controlled bacterial assemblages altered host transcriptional state and metabolite profiles under fixed host genotype (Herrera Paredes et al., 2018; Lebeis et al., 2015). Because these systems control both microbial composition and host genotype, they demonstrate that specific microbial assemblies can drive reproducible regulatory and metabolic outcomes under controlled conditions.
Strigolactones function both as rhizosphere signals that stimulate mycorrhizal fungi and as endogenous hormones regulating plant architecture and resource allocation (Bouwmeester et al., 2007; Gomez-Roldan et al., 2008; Umehara et al., 2008; Delaux et al., 2012). Their dual role positions them as both inputs to and outputs of regulatory networks that link environmental signaling to interactions with plant developmental pathways (Al-Babili & Bouwmeester, 2015; Rasmussen et al., 2012). As their levels change, they reflect upstream conditions while simultaneously altering downstream developmental and metabolic responses. Strigolactones are produced across a broad range of angiosperms, with studies focused mainly on monocots such as rice (Oryza sativa), maize (Zea mays), and sorghum (Sorghum bicolor), as well as dicots including tomato and sunflower, indicating conservation across plant lineages.
They are actively exuded from roots, particularly under phosphorus and nitrogen limitation, where they function as rhizosphere signals that stimulate hyphal branching, mitochondrial activity, and colonization in arbuscular mycorrhizal fungi, thereby facilitating symbiotic establishment (Akiyama et al., 2005; Besserer et al., 2006; Yoneyama et al., 2008; Walker et al., 2019). This exudate function also extends to interactions with other rhizosphere organisms, including the induction of germination in parasitic plants such as Striga and Orobanche, indicating that strigolactones act as context-dependent signals mediating both beneficial and detrimental biotic interactions depending on environmental conditions and community composition (Walker et al., 2019).
Secondary metabolic pathways are coordinated by transcription factor families such as MYB, bHLH, and WRKY, which integrate hormonal and environmental signals to regulate suites of biosynthetic genes (Chezem & Clay, 2016; Cao et al., 2020; Li et al., 2025). MYB transcription factors, in particular, regulate phenylpropanoid metabolism, including flavonoid and lignin biosynthesis, and respond to hormone-mediated signaling triggered by microbial interactions (Chezem & Clay, 2016). Several reviews support microbial effects on hormone balance and transcription factor activity, with downstream changes in secondary metabolite composition commonly interpreted as altered pathway output, though direct flux measurement remains uncommon (Pieterse et al., 2012; Chezem & Clay, 2016; Stringlis et al., 2022). Through induced systemic responses and symbiosis-related signaling, microbial inputs alter hormone balance, which in turn modulates transcription factor activity and redirects metabolic flux across competing biosynthetic pathways (Pieterse et al., 2012; Pieterse et al., 2014).
Wild Ecosystems
The distinction between wild and cultivated medicinal plants is often framed as a comparison between two sources of material. That framing treats ecology as an input variable, analogous to soil type, fertilizer regime, or climate. The evidence reviewed across the prior sections supports a different interpretation. Wild systems are not simply different inputs. They are multi-factor constraints in which multiple variables including microbial diversity, nutrient limitation, competition, and environmental variability are simultaneously active. These factors do not increase complexity step by step. Instead, through interacting constraints on resources, regulation, and signaling, they reduce the range of feasible metabolic states the plant can express.
Wild soils support more complex and chemically interactive plant–microbe systems, a pattern directly observed in Hydrastis canadensis, where root isoquinoline alkaloids selectively altered the behavior of associated fungal taxa, including stimulation of endophytic Fusarium oxysporum growth characteristics and mycotoxin production, while differentially affecting non-endophytic isolates (Tims, 2006). The study also provided an example of how reduced or altered microbial communities may shift functional outcomes, as specific fungal taxa respond differently to the same alkaloid environment, indicating that community composition determines how chemical signals are interpreted. This demonstrates that plant-derived secondary metabolites participate in structuring microbial communities, and conversely, that microbial responses are functionally linked to the plant’s chemical phenotype.
Multiple studies support the conclusion that microbial diversity affects plant–microbe interaction outcomes, including nutrient exchange, disease suppression, and associated plant physiological states, while direct consequences for specific secondary metabolites remain more system-dependent (Delgado-Baquerizo et al., 2016; Mendes et al., 2013; Wagg et al., 2014; Vandenkoornhuyse et al., 2015).
Microbial community composition also feeds back on plant function through metabolite-mediated and microbiome-mediated interactions. Plant-derived compounds such as benzoxazinoids have been shown to restructure associated microbial communities, which in turn alter plant performance and metabolic responses, reinforcing the role of microbial composition as a constraint on plant biochemical outcomes (Kudjordjie et al., 2019). Cultivated soils, particularly those subject to fertilization and chemical inputs, often exhibit reduced microbial diversity and altered community composition, which constrains the range of plant–microbe interactions (van der Heijden et al., 2008).
This is juxtaposed with wild systems, as well as organic and less-managed soils, support more diverse and functionally differentiated mycorrhizal communities, and experimental and field studies show that variation in these communities is associated with changes in plant metabolic traits, including secondary metabolite accumulation and allocation (Verbruggen et al., 2010; Treseder, 2013; Vandenkoornhuyse et al., 2015).
Experiments with grassland and herbaceous model plant species grown in soils conditioned by diverse microbial communities exhibit different growth and defense characteristics compared to those grown in simplified or sterilized soils (Bever et al., 2010). These effects persist even when abiotic conditions are controlled, indicating that microbial community structure itself acts as a constraint on plant function.
Reciprocal soil conditioning experiments extend this approach by demonstrating that microbial community history influences subsequent plant metabolism. Plants grown in soils conditioned by different species or management regimes exhibit distinct gene expression profiles and metabolite outputs even when transferred to identical abiotic conditions but different microbial environment, indicating that microbial legacy effects act through regulatory pathways rather than direct nutrient differences (Bever et al., 2010; Wagg et al., 2014; Trivedi et al., 2020; Pang et al., 2021).
Soil sterilization and re-inoculation experiments show that removing native microbiota alters plant-associated metabolic function and microbial community structure, while reintroduction of microbial communities restores key microbial activities and plant physiological processes linked to nutrient cycling and growth (Qin et al., 2014; Zhang et al., 2019). Direct restoration of specific secondary metabolite profiles has not been resolved within a single experimental system, but these findings support a causal role for microbiome composition in regulating plant metabolic state.
Temporal or seasonal variability adds another dimension. Wild systems are subject to fluctuations in moisture, temperature, light intensity, water status, and nutrient availability, as well as seasonal changes in microbial activity (Bardgett & Caruso, 2020; Classen et al., 2015). These factors differentially regulate individual ginsenosides and their relative abundances, producing coordinated increases and decreases across compound classes rather than uniform changes in total content (Wu et al., 2024).
These fluctuations require plants to operate within a dynamic range of conditions, reinforcing flexible regulatory mechanisms. Cultivated systems often aim to minimize variability, creating more stable but narrower environmental conditions through practices such as irrigation, fertilization, and soil management (Matson et al., 1997; Tilman et al., 2002). While this can improve yield predictability, it may also reduce the range of metabolic states the plant experiences, leading to more uniform but potentially less complex metabolite profiles (Classen et al., 2015; Bardgett & Caruso, 2020).
References
1. Akiyama, K., Matsuzaki, K., & Hayashi, H. (2005). Plant sesquiterpenes induce hyphal branching in arbuscular mycorrhizal fungi. Nature, 435(7043), 824–827. https://doi.org/10.1038/nature03608
2. Al-Babili, S., & Bouwmeester, H. J. (2015). Strigolactones, a novel carotenoid-derived plant hormone. Annual Review of Plant Biology, 66, 161–186. https://doi.org/10.1146/annurev-arplant-043014-114759
3. Bardgett, R. D., & Caruso, T. (2020). Soil microbial community responses to climate extremes: Resistance, resilience and transitions to alternative states. Philosophical Transactions of the Royal Society B, 375(1794), 20190112. https://doi.org/10.1098/rstb.2019.0112
4. Besserer, A., Puech-Pagès, V., Kiefer, P., Gomez-Roldan, V., Jauneau, A., Roy, S., Portais, J.-C., Roux, C., Bécard, G., & Séjalon-Delmas, N. (2006). Strigolactones stimulate arbuscular mycorrhizal fungi by activating mitochondria. PLoS Biology, 4(7), e226. https://doi.org/10.1371/journal.pbio.0040226
5. Bever, J. D., Platt, T. G., & Morton, E. R. (2010). Microbial population and community dynamics on plant roots and their feedbacks on plant communities. Annual Review of Microbiology, 64, 321–347. https://doi.org/10.1146/annurev.micro.112408.134257
6. Bouwmeester, H. J., Roux, C., López-Ráez, J. A., & Bécard, G. (2007). Rhizosphere communication of plants, parasitic plants and AM fungi. Trends in Plant Science, 12(5), 224–230. https://doi.org/10.1016/j.tplants.2007.03.009
7. Cao, Y., Li, K., Li, Y., Zhao, X., & Wang, L. (2020). MYB transcription factors as regulators of secondary metabolism in plants. Biology, 9(3), 61. https://doi.org/10.3390/biology9030061
8. Chezem, W. R., & Clay, N. K. (2016). Regulation of plant secondary metabolism and associated specialized cell development by MYBs and bHLHs. Phytochemistry, 131, 26–43. https://doi.org/10.1016/j.phytochem.2016.08.006
9. Classen, A. T., Sundqvist, M. K., Henning, J. A., Newman, G. S., Moore, J. A., Cregger, M. A., Moorhead, L. C., & Patterson, C. M. (2015). Direct and indirect effects of climate change on soil microbial and soil community structure and function. Global Change Biology, 21(3), 957–971. https://doi.org/10.1111/gcb.12821
10. Delaux, P.-M., Xie, X., Timme, R. E., et al. (2012). Origin of strigolactones in the green lineage. New Phytologist, 195(4), 857–871. https://doi.org/10.1111/j.1469-8137.2012.04209.x
11. Delgado-Baquerizo, M., Reich, P. B., Khachane, A. N., Campbell, C. D., Thomas, N., Freitag, T. E., Abu Al-Soud, W., Sørensen, S., Bardgett, R. D., & Singh, B. K. (2016). Microbial diversity drives multifunctionality in terrestrial ecosystems. Nature Communications, 7, 10541. https://doi.org/10.1038/ncomms10541
12. Gomez-Roldan, V., Fermas, S., Brewer, P. B., Puech-Pagès, V., Dun, E. A., Pillot, J.-P., Letisse, F., Matusova, R., Danoun, S., Portais, J.-C., Bouwmeester, H., Bécard, G., Beveridge, C. A., Rameau, C., & Rochange, S. F. (2008). Strigolactone inhibition of shoot branching. Nature, 455(7210), 189–194. https://doi.org/10.1038/nature07271
13. Herrera Paredes, S., Gao, T., Law, T. F., Finkel, O. M., Mucyn, T., Teixeira, P. J. P. L., Salas-González, I., Feltcher, M. E., Powers, M. J., Shank, E. A., Jones, C. D., & Dangl, J. L. (2018). Design of synthetic bacterial communities for predictable plant phenotypes. PLoS Biology, 16(2), e2003962. https://doi.org/10.1371/journal.pbio.2003962
14. Koprivova, A., & Kopriva, S. (2022). Plant secondary metabolites altering root microbiome composition and function. Current Opinion in Plant Biology, 67, 102227. https://doi.org/10.1016/j.pbi.2022.102227
15. Kudjordjie, E. N., Sapkota, R., Steffensen, S. K., Fomsgaard, I. S., & Nicolaisen, M. (2019). Maize synthesized benzoxazinoids affect the host associated microbiome. Microbiome, 7, 59. https://doi.org/10.1186/s40168-019-0660-2
16. Lebeis, S. L., Paredes, S. H., Lundberg, D. S., Breakfield, N., Gehring, J., McDonald, M., Malfatti, S., Del Rio, T. G., Jones, C. D., Tringe, S. G., & Dangl, J. L. (2015). Salicylic acid modulates colonization of the root microbiome by specific bacterial taxa. Science, 349(6250), 860–864. https://doi.org/10.1126/science.aaa8764
17. Li, H., Chen, N., Zhang, H., & Xu, D. (2025). Multidimensional regulation of transcription factors: Decoding the comprehensive signals of plant secondary metabolism. Frontiers in Plant Science, 16, 1522278. https://doi.org/10.3389/fpls.2025.1522278
18. Luginbuehl, L. H., Menard, G. N., Kurup, S., Van Erp, H., Radhakrishnan, G. V., Breakspear, A., Oldroyd, G. E. D., & Eastmond, P. J. (2017). Fatty acids in arbuscular mycorrhizal fungi are synthesized by the host plant. Science, 356(6343), 1175–1178. https://doi.org/10.1126/science.aan0081
19. Maillet, F., Poinsot, V., André, O., et al. (2011). Fungal lipochitooligosaccharide signals in mycorrhiza. Nature, 469(7328), 58–63. https://doi.org/10.1038/nature09622
20. Mandal, S., Upadhyay, S., Wajid, S., Ram, M., Jain, D. C., Singh, V. P., Abdin, M. Z., & Kapoor, R. (2015). Arbuscular mycorrhiza increase artemisinin accumulation in Artemisia annua by higher expression of key biosynthesis genes via enhanced jasmonic acid levels. Mycorrhiza, 25(5), 345–357. https://doi.org/10.1007/s00572-014-0614-3
21. Matson, P. A., Parton, W. J., Power, A. G., & Swift, M. J. (1997). Agricultural intensification and ecosystem properties. Science, 277(5325), 504–509. https://doi.org/10.1126/science.277.5325.504
22. Mendes, R., Garbeva, P., & Raaijmakers, J. M. (2013). The rhizosphere microbiome: Significance of plant beneficial, plant pathogenic, and human pathogenic microorganisms. FEMS Microbiology Reviews, 37(5), 634–663. https://doi.org/10.1111/1574-6976.12028
23. Oldroyd, G. E. D. (2013). Speak, friend, and enter: Signalling systems that promote beneficial symbiotic associations in plants. Nature Reviews Microbiology, 11(4), 252–263. https://doi.org/10.1038/nrmicro2990
24. Pang, Z., Chen, J., Wang, T., Gao, C., Li, Z., Guo, L., Xu, J., & Cheng, Y. (2021). Linking plant secondary metabolites and plant microbiomes: A review. Frontiers in Plant Science, 12, 621276. https://doi.org/10.3389/fpls.2021.621276
25. Pieterse, C. M. J., Van der Does, D., Zamioudis, C., Leon-Reyes, A., & Van Wees, S. C. M. (2012). Hormonal modulation of plant immunity. Annual Review of Cell and Developmental Biology, 28, 489–521. https://doi.org/10.1146/annurev-cellbio-092910-154055
26. Pieterse, C. M. J., Zamioudis, C., Berendsen, R. L., Weller, D. M., Van Wees, S. C. M., & Bakker, P. A. H. M. (2014). Induced systemic resistance by beneficial microbes. Annual Review of Phytopathology, 52, 347–375. https://doi.org/10.1146/annurev-phyto-082712-102340
27. Qin, S. Q., Xing, K., Jiang, J. H., Xu, L. H., & Li, W. J. (2014). Effects of soil sterilization and biological agent inoculation on root respiratory metabolism and plant growth. Scientia Horticulturae, 174, 118–125. https://doi.org/10.1016/j.scienta.2014.05.006
28. Rasmussen, A., Mason, M. G., De Cuyper, C., Brewer, P. B., Herold, S., Agusti, J., Geelen, D., Greb, T., Goormachtig, S., Beeckman, T., & Beveridge, C. A. (2012). Strigolactones suppress adventitious rooting in Arabidopsis and pea. Plant Physiology, 158(4), 1976–1987. https://doi.org/10.1104/pp.111.187104
29. Tilman, D., Cassman, K. G., Matson, P. A., Naylor, R., & Polasky, S. (2002). Agricultural sustainability and intensive production practices. Nature, 418(6898), 671–677. https://doi.org/10.1038/nature01014
30. Tims, M. C. (2006). The chemical ecology of Hydrastis canadensis L. (Ranunculaceae): Effects of root isoquinoline alkaloids on the Hydrastis endophyte, Fusarium oxysporum (Doctoral dissertation, University of Maryland, College Park).
31. Treseder, K. K. (2013). The extent of mycorrhizal colonization of roots and its influence on plant growth and phosphorus content. Plant and Soil, 371(1–2), 1–13. https://doi.org/10.1007/s11104-013-1681-5
32. Trivedi, P., Leach, J. E., Tringe, S. G., Sa, T., & Singh, B. K. (2020). Plant–microbiome interactions: From community assembly to plant health. Nature Reviews Microbiology, 18(11), 607–621. https://doi.org/10.1038/s41579-020-0412-0
33. Umehara, M., Hanada, A., Yoshida, S., Akiyama, K., Arite, T., Takeda-Kamiya, N., Magome, H., Kamiya, Y., Shirasu, K., Yoneyama, K., Kyozuka, J., & Yamaguchi, S. (2008). Inhibition of shoot branching by new terpenoid plant hormones. Nature, 455(7210), 195–200. https://doi.org/10.1038/nature07272
34. Vandenkoornhuyse, P., Quaiser, A., Duhamel, M., Le Van, A., & Dufresne, A. (2015). The importance of the microbiome of the plant holobiont. New Phytologist, 206(4), 1196–1206. https://doi.org/10.1111/nph.13312
35. van der Heijden, M. G. A., Bardgett, R. D., & van Straalen, N. M. (2008). The unseen majority: Soil microbes as drivers of plant diversity and productivity in terrestrial ecosystems. Ecology Letters, 11(3), 296–310. https://doi.org/10.1111/j.1461-0248.2007.01139.x
36. Verbruggen, E., Röling, W. F. M., Gamper, H. A., et al. (2010). Organic farming and mycorrhizal communities. New Phytologist, 186(4), 968–979. https://doi.org/10.1111/j.1469-8137.2010.03230.x
37. Wagg, C., Bender, S. F., Widmer, F., & van der Heijden, M. G. A. (2014). Soil biodiversity and soil community composition determine ecosystem multifunctionality. Proceedings of the National Academy of Sciences, 111(14), 5266–5270. https://doi.org/10.1073/pnas.1320054111
38. Walker, C. H., Siu-Ting, K., Taylor, A., O’Connell, M. J., Bennett, T., & Leyser, O. (2019). Strigolactone synthesis is ancestral in land plants, but canonical strigolactone signalling is a flowering plant innovation. BMC Biology, 17, 70. https://doi.org/10.1186/s12915-019-0689-6
39. Wang, W., Shi, J., Xie, Q., Jiang, Y., Yu, N., & Wang, E. (2018). Nutrient exchange and regulation in arbuscular mycorrhizal symbiosis. Molecular Plant, 11(9), 1140–1151. https://doi.org/10.1016/j.molp.2018.06.001
40. Wu, D., Xiong, F., Wang, H., Liu, S., Zhu, J., Zhao, D., Yang, J., Ma, W., Guo, L., & Kang, C. (2024). Temperature seasonality and soil phosphorus availability shape ginseng quality via regulating ginsenoside contents. BMC Plant Biology, 24, 824. https://doi.org/10.1186/s12870-024-05518-2
41. Yoneyama, K., Xie, X., Kisugi, T., Nomura, T., Sekimoto, H., Yokota,T., & Yoneyama, K. (2008). Nitrogen deficiency as well as phosphorus deficiency in sorghum promotes the production and exudation of strigolactones. Planta, 227(1), 125–132. https://doi.org/10.1007/s00425-007-0600-8
42. Zhang, B., Zhang, J., Liu, Y., Guo, Y., & Zhang, X. (2019). Soil sterilization leads to re-colonization of a healthier rhizosphere microbiome. Rhizosphere, 12, 100176. https://doi.org/10.1016/j.rhisph.2019.100176
43. Zhang, F., Li, M., Guo, K., Zhang, P., & Wang, L. (2020). Arbuscular mycorrhizal fungi increase artemisinin accumulation by regulating the expression of key biosynthetic genes and jasmonate signaling in Artemisia annua. Industrial Crops and Products, 144, 112047. https://doi.org/10.1016/j.indcrop.2019.112047