A review of flavonoids at the crossroads of plant defense: integrating biotic and abiotic stress tolerance through AI- and CRISPR/Cas-guided metabolic reprogramming
A roadmap for predictive reprogramming of flavonoid networks under combined stress and the development of crops with improved resilience to increasingly complex environmental conditions is outlined.
Abstract
Flavonoids are multifunctional phenylpropanoid-derived metabolites that occupy a central position in plant adaptation to environmental stress. Beyond their established roles in antioxidant protection, they contribute to defense against pathogens and herbivores, signaling processes, and physiological acclimation to adverse environmental conditions. Although flavonoid responses to individual biotic or abiotic stresses have been extensively investigated, considerably less attention has been given to how flavonoid-associated regulatory networks function when multiple stresses occur simultaneously. This gap is particularly important because crops in agricultural systems are routinely exposed to overlapping biotic and abiotic challenges that generate distinct physiological, transcriptional, and metabolic responses. This review synthesizes current knowledge of flavonoid biosynthesis, structure-activity relationships, and the regulatory mechanisms governing flavonoid accumulation under diverse stress conditions. Particular emphasis is placed on the reorganization of flavonoid-associated networks under combined stress, including signaling crosstalk, pathway competition, metabolic trade-offs, and flux allocation that collectively shape adaptive responses. This review further evaluates how artificial intelligence can support identification of regulatory targets and pathway bottlenecks, how integration with CRISPR/Cas technologies may facilitate more precise manipulation of flavonoid biosynthesis, and how iterative Design–Build–Test–Learn (DBTL) frameworks could improve predictive flavonoid engineering through continuous integration of computational prediction and experimental validation. By integrating advances in stress biology, computational prediction, genome engineering, and iterative DBTL frameworks, this review outlines a roadmap for predictive reprogramming of flavonoid networks under combined stress and the development of crops with improved resilience to increasingly complex environmental conditions.
Drought stress is among the most severe environmental constraints limiting plant growth, productivity and ecosystem stability worldwide. It disrupts cellular homeostasis, impairs photosynthesis, induces oxidative damage and alters metabolite profiles. In response, plants activate coordinated physiological and metabolic responses that reprogram carbon and nitrogen allocation toward protective functions. A major component of this adaptive response is the enhanced production of plant secondary metabolites, which contribute to stress tolerance through integrated biochemical, physiological and ecological mechanisms. This review synthesizes the major classes of drought-responsive secondary metabolites including phenylpropanoids, flavonoids, terpenoids, alkaloids and glucosinolates, and evaluates their biosynthetic pathways, regulatory networks and functional roles in drought adaptation. These metabolites contribute to antioxidant defense, membrane stabilization, osmotic adjustment, lignification and hormonal signaling, maintaining cellular homeostasis under drought stress. Their biosynthesis is coordinated through carbon and nitrogen reallocation via the shikimate, mevalonate, and methylerythritol phosphate pathways, and regulated by transcription factors, abscisic acid signaling and epigenetic modifications. Unlike previous reviews that discuss metabolite classes independently, this review integrates carbon–nitrogen allocation, metabolic trade-offs, regulatory networks and ecological interactions into a systems-level framework for understanding drought adaptation. Therefore, integrating molecular insights with breeding and metabolic engineering approaches facilitates the development of climate-resilient crops adapted to increasingly water-limited environments, supporting global food security and climate adaptation efforts.
This synthesis provides a framework for translating mechanistic hormonal insights into field-applicable cultivars to ensure global food security and proposes a systems-level roadmap for developing climate-resilient rice cultivars capable of maintaining yield stability across a volatile combinatorial stress landscape.
Shuixing Zhu, Zhu Jing, Dikhnah Alshehri et al.· Frontiers in Plant Science· 0 citations
Traditional breeding and modern techniques like Marker-Assisted Selection, Genetic Engineering, Genome Editing and Genomic Selection are used to identify and integrate desirable traits into new crop varieties, enabling breeders to develop more robust and stable crops.
This review systematizes current knowledge on the types of CAS, their interactions, and their impacts on plant physiological, molecular, and microbiological processes, and extrapolates from established mechanisms to propose how microbes may mitigate combined stresses.
O. Lastochkina, A. Avalbaev, A. Lubyanova et al.· Applied Biochemistry and Mic...· 0 citations
Abiotic stress, including drought, salinity, heavy metals, and extreme temperatures, severely limits plant growth, productivity, and survival. These stresses frequently occur simultaneously and disrupt cellular homeostasis, photosynthesis, and metabolic processes. To cope with such adverse conditions, plants activate complex physiological, biochemical, and molecular defense mechanisms. Among the emerging stress-related signaling compounds, β-cyclocitral, a β-carotene-derived apocarotenoid, has gained significant attention due to its crucial role in plant stress adaptation. β-Cyclocitral enhances photoprotection by scavenging free radicals and reducing singlet oxygen-mediated damage to photosynthetic machinery. It also modulates reactive oxygen species (ROS) homeostasis through the activation of antioxidant defense systems, thereby minimizing oxidative stress. In parallel, key phytohormones such as abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA) regulate diverse stress-responsive pathways that improve plant tolerance and defense. Increasing evidence suggests that β-cyclocitral interacts closely with these hormonal signaling networks to coordinate stress responses and metabolic adjustments. This review highlights recent advances in the biosynthesis, physiological functions, and signaling roles of β-cyclocitral, with particular emphasis on its mechanistic crosstalk with ABA, JA, and SA pathways in enhancing abiotic stress tolerance in plants.
P. Alam, M. Faizan, Thamer H. Albalawi et al.· Frontiers in Plant Science· 0 citations
