Metabolomics reveal drought-stress responses in guayule, a semi-arid rubber crop

INTRODUCTION: Natural rubber is crucial for many industries, and guayule, (Parthenium argentatum A. Gray, is a promising alternative source for rubber in the arid and semi-arid regions. Rubber concentration production in guayule increases under drought stress, but the metabolic reasons remain unclear. OBJECTIVES AND METHODS: Using untargeted metabolomic approach, this study analyzed drought-induced metabolomic changes in two guayule cultivars, AZ-4 and CAL-2, focusing on key metabolites linked to resin and rubber biosynthesis. RESULTS: We identified 53 drought-responsive metabolites, with 27 differing significantly between cultivars. AZ 4 showed increased stress signaling molecules and precursor metabolites, indicating rapid metabolic activation under drought, while CAL 2 accumulated triterpenoid saponins and lysophospholipids, suggesting membrane stabilization and long term osmoprotective defense. Under drought, both cultivars shared depletion of 4'-phosphopantothenoylcysteine, indicating a potential bottleneck in Coenzyme A biosynthesis. Reduced ubiquinone-1 further suggested a diversion of isoprenoid precursors away from respiration and toward secondary metabolism. This shift is linked to activation of the MVA and MEP pathways, which enhanced flux into rubber and resin biosynthesis rather than ubiquinone production. Although cis-1,4-polyisoprene was not directly measured, the observed increases in key terpenoid precursors and pathway‑associated metabolites are consistent with enhanced flux toward rubber biosynthesis under drought conditions. CONCLUSION: Divergent metabolic patterns reflect genetic and biochemical diversity: AZ 4 favors rapid stress signaling and precursor synthesis, whereas CAL 2 emphasizes antioxidant and osmoprotective mechanisms. These biomarkers make them valuable for breeding drought-tolerant, and high-yield guayule germplasm to advance sustainable rubber production in dry regions.