The hidden role of amino acids and secondary metabolites in plant drought tolerance

Drought stress (DS) severely threatens global crop productivity by disrupting key physiological, biochemical, and metabolic processes during plant development, ultimately leading to substantial yield losses. Though plants have evolved various adaptive mechanisms, their effectiveness remains species- and environment-dependent. Recent research increasingly explores green chemical interventions, particularly the roles of amino acids (AAs) and secondary metabolites (SMs) in enhancing DS tolerance. These bioactive compounds, including proline, glycine betaine, alanine, γ-aminobutyric acid, phenylalanine, phenolics, terpenes, and nitrogen-containing compounds, play critical roles in osmoprotection, antioxidative defense, cellular homeostasis, transcriptional regulation, and stress-responsive gene expression. Nevertheless, undetermined paradoxes persist (e.g., proline/lignin accumulation can be shielding or growth-limiting depending on species and stress context), along with species-specific AA/SM responses, and the lack of integrated AA-SM flux examinations. This also features that AAs and SMs act as context-specific rather than universally beneficial compounds. To address these gaps, we propose specific, verifiable postulates (e.g., isotope tracking of AA-derived carbon into SM pathways and conditional genetic perturbations of biosynthetic nodes under field DS). We also highlight advances in genetic engineering tools to optimize AA and SM biosynthesis and regulation. Overall, this review synthesizes conceptual innovations and proposes future directions for developing drought-smart crop plants that can drive targeted metabolic interventions for future food security. We anticipate that integrating metabolic flux testing, omics-driven gene-metabolite mapping, and field validation will help bridge the gap between mechanistic insights and field applications.