A comprehensive mechanistic analysis of emerging pharmaceutical pollutants' stress response in plants is crucial to understand their chronic impact on food-chain contamination and agricultural productivity. To unravel this at the systems level, stress response of carbamazepine (CBZ), an emerging recalcitrant anticonvulsant pollutant, was simulated in tomato. For this, an updated genome-scale metabolic model of tomato leaf, CBZᵢSL3433, augmented with CBZ detoxification reactions based on green-liver concept was developed. Under phototrophic conditions, CBZᵢSL3433 predicted energy and co-factor competition-induced biomass reduction under CBZ stress. Further, the study provides an in silico mechanistic insight for abiotic stress response induced by CBZ in tomato with altered flux states in nutrient assimilation, synthesis of key precursors of leaf biomass, and secondary metabolites. Additionally, potential ameliorative effects of biostimulants such as proline, spermine, glycerol, and ethanol were investigated through model predictions. Through systematic computational analysis, 154 significantly altered reactions were identified in the presence of CBZ stress, of which 92% were ameliorated with biostimulants. Notably, based on simulations, amino acid biosynthesis was the most significantly altered pathway under CBZ stress. Overall, the proposed framework can aid in screening and developing rational strategies to maintain agricultural yields amid rising plant stress due to such anthropogenic pollutants.
Srinivasan et al. (Mon,) studied this question.