Investigating the impact of carbamazepine on tomato plant metabolism using genome-scale metabolic modelling

investigating-the-impact-of-carbamazepine-on-tomato-plant-metabolism-using-genome-scale-metabolic-modelling
Investigating the impact of carbamazepine on tomato plant metabolism using genome-scale metabolic modelling

References

  1. Carter, L. J., Chefetz, B., Abdeen, Z. & Boxall, A. Emerging investigator series: towards a framework for establishing the impacts of pharmaceuticals in wastewater irrigation systems on agro-ecosystems and human health. Environ. Sci. Process Impacts. 21, 605–622 (2019).

    Google Scholar 

  2. Patel, M. et al. Pharmaceuticals of Emerging Concern in Aquatic Systems: Chemistry, Occurrence, Effects, and Removal Methods. Chem. Rev. 119, 3510–3673 (2019).

    Google Scholar 

  3. Poudel, S., Shrestha, A., Kandel, N., Adhikari, S. & Paudel, S. R. A Review of Reclaimed Water Reuse for Irrigation in South Asian Countries. ACS ES&T Wat. 3, 3790–3806 (2023).

    Google Scholar 

  4. Wang, Y. et al. Antiepileptic drug carbamazepine promotes horizontal transfer of plasmid-borne multi-antibiotic resistance genes within and across bacterial genera. ISME J. 13, 509–522 (2019).

    Google Scholar 

  5. Nguyen, M. K. et al. Occurrence, fate, and potential risk of pharmaceutical pollutants in agriculture: Challenges and environmentally friendly solutions. Sci. Total Environ. 899, 165323 (2023).

    Google Scholar 

  6. Garduño-Jiménez, A. L. & Carter, L. J. Insights into mode of action mediated responses following pharmaceutical uptake and accumulation in plants. Front. Agron. 5, 1293555 (2024).

    Google Scholar 

  7. Machado, T. M., Töpfer, N. & Soltani, F. Metabolic modelling: Insights into the machine room of plant metabolism. J Plant. Physiol. 154584 (2025).

  8. Cordes, H., Thiel, C., Baier, V., Blank, L. M. & Kuepfer, L. Integration of genome-scale metabolic networks into whole-body PBPK models shows phenotype-specific cases of drug-induced metabolic perturbation. npj Syst. Biol. Appl. 4, 10 (2018).

    Google Scholar 

  9. Sahoo, S., Haraldsdóttir, H. S., Fleming, R. M. T. & Thiele, I. Modeling the effects of commonly used drugs on human metabolism. FEBS J. 282, 297–317 (2015).

    Google Scholar 

  10. Sandermann, H., Diesperger, H. & Scheel, D. Metabolism of Xenobiotics by Plant Cell Cultures. in Plant Tissue Culture and Its Bio-technological Application (eds Barz, W., Reinhard, E. & Zenk, M. H.) Proceedings in Life Sciences 178–196 Springer, Berlin, Heidelberg, (1977).

  11. Malchi, T., Eyal, S., Czosnek, H., Shenker, M. & Chefetz, B. Plant pharmacology: Insights into in-planta kinetic and dynamic processes of xenobiotics. Crit. Rev. Environ. Sci. Technol. 52, 3525–3546 (2022).

    Google Scholar 

  12. Coleman, J., Blake-Kalff, M. & Davies, E. Detoxification of xenobiotics by plants: chemical modification and vacuolar compartmentation. Trends Plant Sci. 2, 144–151 (1997).

    Google Scholar 

  13. Kaushik, G. et al. Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers. Biochem. Biophys. Res. Commun. 474 (2), 291–295 (2016).

    Google Scholar 

  14. Gorovits, R., Sobol, I., Akama, K., Chefetz, B. & Czosnek, H. Pharmaceuticals in treated wastewater induce a stress response in tomato plants. Sci. Rep. 10, 1856 (2020).

    Google Scholar 

  15. Riemenschneider, C., Seiwert, B., Moeder, M., Schwarz, D. & Reemtsma, T. Extensive Transformation of the Pharmaceutical Carbamazepine Following Uptake into Intact Tomato Plants. Environ. Sci. Technol. 51, 6100–6109 (2017).

    Google Scholar 

  16. Gerlin, L., Cottret, L., Escourrou, A., Genin, S. & Baroukh, C. A multi-organ metabolic model of tomato predicts plant responses to nutritional and genetic perturbations. Plant. Physiol. 188, 1709–1723 (2022).

    Google Scholar 

  17. Shiade, S. R. G. et al. Plant metabolites and signaling pathways in response to biotic and abiotic stresses: Exploring bio stimulant applications. Plant. Stress. 12, 100454 (2024).

    Google Scholar 

  18. Dordio, A. V. et al. Evaluation of carbamazepine uptake and metabolization by Typha spp., a plant with potential use in phytotreatment. Bioresour. Technol. 102, 7827–7834 (2011).

    Google Scholar 

  19. Schröder, P. Exploiting Plant Metabolism for the Phytoremediation of Organic Xenobiotics. in Phytoremediation: Methods and Reviews (ed. Willey, N.) Methods in Biotechnology 23, 251–263 (Humana Press, Totowa, NJ, 2007).

  20. Lu, Z. Y. et al. Unmasking Spatial Heterogeneity in Phytotoxicology Mechanisms Induced by Carbamazepine by Mass Spectrometry Imaging and Multiomics Analyses. Environ. Sci. Technol. 58, 13986–13994 (2024).

    Google Scholar 

  21. Sauvêtre, A., May, R., Harpaintner, R., Poschenrieder, C. & Schröder, P. Metabolism of carbamazepine in plant roots and endophytic rhizobacteria isolated from Phragmites australis. J. Hazard. Mater. 342, 85–95 (2018).

    Google Scholar 

  22. Lieven, C. et al. MEMOTE for standardized genome-scale metabolic model testing. Nat. Biotechnol. 38, 272–276 (2020).

    Google Scholar 

  23. Raman, K. et al. FROG analysis Ensures the Reproducibility of Genome Scale Metabolic Models. Preprint bioRxiv. https://doi.org/10.1101/2024.09.24.614797 (2024).

    Google Scholar 

  24. Heirendt, L. et al. Creation and analysis of biochemical constraint-based models using the COBRA Toolbox v.3.0. Nat. Protoc. 14, 639–702 (2019).

    Google Scholar 

  25. Nanda, P., Patra, P., Das, M. & Ghosh, A. Reconstruction and analysis of genome-scale metabolic model of weak Crabtree positive yeast Lachancea kluyveri. Sci. Rep. 10, 16314 (2020).

    Google Scholar 

  26. García-García, A. L. et al. Pure Organic Active Compounds Against Abiotic Stress: A Biostimulant Overview. Front. Plant Sci. 11, 575829 (2020).

    Google Scholar 

  27. Jiménez-Arias, D. et al. A Beginner’s Guide to Osmoprotection by Biostimulants. Plants. 10, 363 (2021).

    Google Scholar 

  28. Thorn, C. F. et al. PharmGKB summary: carbamazepine pathway. Pharmacogenet. Genomics. 21, 906 (2011).

    Google Scholar 

  29. Whirl-Carrillo, M. et al. An Evidence-Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine. Clin. Pharmacol. Ther. 110, 563–572 (2021).

    Google Scholar 

  30. Meech, R., Miners, J. O., Lewis, B. C. & Mackenzie, P. I. The glycosidation of xenobiotics and endogenous compounds: Versatility and redundancy in the UDP glycosyltransferase superfamily. Pharmacol. Ther. 134, 200–218 (2012).

    Google Scholar 

  31. Leitão, I. et al. Stress response of lettuce (Lactuca sativa) to environmental contamination with selected pharmaceuticals: A proteomic study. J. Proteomics. 245, 104291 (2021).

    Google Scholar 

  32. Landa, P., Prerostova, S., Langhansova, L., Marsik, P. & Vanek, T. Transcriptomic response of Arabidopsis thaliana (L.) Heynh. Roots to ibuprofen. Int. J. Phytoremediation. 19, 695–700 (2017).

    Google Scholar 

  33. Landa, P. et al. Transcriptomic response of Arabidopsis thaliana roots to naproxen and praziquantel. Ecotox. Environ. Safe. 166, 301–310 (2018).

    Google Scholar 

  34. Righetti, L. et al. Thinking Out of the Box: On the Ability of Zea mays L. to Biotrasform Aflatoxin B1 Into Its Modified Forms. Front. Plant Sci. 11, 599158 (2021).

    Google Scholar 

  35. Zhang, Y. et al. Enhanced phytoremediation of mixed heavy metal (mercury)–organic pollutants (trichloroethylene) with transgenic alfalfa co-expressing glutathione S-transferase and human P450 2E1. J. Hazard. Mater. 260, 1100–1107 (2013).

    Google Scholar 

  36. Groot, C. C. de, Marcelis, L. F. M., Boogaard, R. van den & Lambers, H. Interactive effects of nitrogen and irradiance on growth and partitioning of dry mass and nitrogen in young tomato plants. Funct. Plant Biol. 29, 1319–1328 (2002).

    Google Scholar 

  37. Carter, L. J., Williams, M., Böttcher, C. & Kookana, R. S. Uptake of Pharmaceuticals Influences Plant Development and Affects Nutrient and Hormone Homeostases. Environ. Sci. Technol. 49, 12509–12518 (2015).

    Google Scholar 

  38. Leitão, I. et al. Antioxidative response of lettuce (Lactuca sativa) to carbamazepine-induced stress. Environ. Sci. Pollut. Res. 28, 45920–45932 (2021).

    Google Scholar 

  39. Knudsen, C., Gallage, N. J., Hansen, C. C., Møller, B. L. & Laursen, T. Dynamic metabolic solutions to the sessile life style of plants. Nat. Prod. Rep. 35, 1140–1155 (2018).

    Google Scholar 

  40. Shameer, S., Ratcliffe, R. G. & Sweetlove, L. J. Leaf Energy Balance Requires Mitochondrial Respiration and Export of Chloroplast NADPH in the Light. Plant Physiol. 180, 1947–1961 (2019).

    Google Scholar 

  41. Varma, A. & Palsson, B. O. Metabolic Flux Balancing: Basic Concepts, Scientific and Practical Use. Nat. Biotechnol. 12, 994–998 (1994).

    Google Scholar 

  42. Kauffman, K. J., Prakash, P. & Edwards, J. S. Advances in flux balance analysis. Curr. Opin. Biotechnol. 14, 491–496 (2003).

    Google Scholar 

  43. Raman, K. & Chandra, N. Flux balance analysis of biological systems: applications and challenges. Brief. Bioinform. 10, 435–449 (2009).

    Google Scholar 

  44. Wahman, R., Sauvêtre, A., Schröder, P., Moser, S. & Letzel, T. Untargeted Metabolomics Studies on Drug-Incubated Phragmites australis Profiles. Metabolites. 11, 2 (2020).

    Google Scholar 

  45. Chowdhury, N. B. et al. Dissecting the metabolic reprogramming of maize root under nitrogen-deficient stress conditions. J. Exp. Bot. 73, 275–291 (2022).

    Google Scholar 

  46. Knight, E. R., Carter, L. J. & McLaughlin, M. J. Bioaccumulation, uptake, and toxicity of carbamazepine in soil–plant systems. Environ. Toxicol. Chem. 37, 1122–1130 (2018).

    Google Scholar 

  47. Voss, I., Sunil, B., Scheibe, R. & Raghavendra, A. S. Emerging concept for the role of photorespiration as an important part of abiotic stress response. Plant Biol. 15, 713–722 (2013).

    Google Scholar 

  48. Akram, N. A., Shafiq, F. & Ashraf, M. Ascorbic Acid-A Potential Oxidant Scavenger and Its Role in Plant Development and Abiotic Stress Tolerance. Front. Plant Sci. 8, 613 (2017).

    Google Scholar 

  49. Ofaim, S. et al. Genome-scale reconstruction of Paenarthrobacter aurescens TC1 metabolic model towards the study of atrazine bioremediation. Sci. Rep. 10, 13019 (2020).

    Google Scholar 

  50. Dhakar, K. et al. Strategies for Enhancing in vitro Degradation of Linuron by Variovorax sp. Strain SRS 16 Under the Guidance of Metabolic Modeling. Front. Bioeng. Biotechnol. 9, 602464 (2021).

    Google Scholar 

  51. Kahlaoui, B. et al. Response of two tomato cultivars to field-applied proline under irrigation with saline water: Growth, chlorophyll fluorescence and nutritional aspects. Photosynthetica. 52, 421–429 (2014).

    Google Scholar 

  52. Pascual, L. S., López-Climent, M. F., Segarra-Medina, C., Gómez-Cadenas, A. & Zandalinas, S. I. Exogenous spermine alleviates the negative effects of combined salinity and paraquat in tomato plants by decreasing stress-induced oxidative damage. Front. Plant Sci. 14, 1193207 (2023).

    Google Scholar 

  53. Todaka, D. et al. Application of ethanol alleviates heat damage to leaf growth and yield in tomato. Front. Plant Sci. 15, 1325365 (2024).

    Google Scholar 

  54. M. Ali, R., Elfeky, S. S. & Abbas, H. Response of Salt Stressed Ricinus communis L. To Exogenous Application of Glycerol and/or Aspartic acid. J. Biol. Sci. 8, 171–175 (2008).

  55. Kaya, C., Aydemir, S., Sonmez, O., Ashraf, M. & Dikilitas, M. Regulation of growth and some key physiological processes in salt-stressed maize (Zea mays L.) plants by exogenous application of asparagine and glycerol. Acta Bot. Croat. 72, 157–168 (2013).

    Google Scholar 

  56. Raoufi, A., Rahemi, M. & Akbari, M. Glycerol foliar application improves salt tolerance in three pistachio rootstocks. J. Saudi Soc. Agri Sci. 19 (6), 426–437 (2020).

    Google Scholar 

  57. Hosseinifard, M. et al. Contribution of Exogenous Proline to Abiotic Stresses Tolerance in Plants: A Review. Int. J. Mol. Sci. 23, 5186 (2022).

    Google Scholar 

  58. Li, Z. et al. Global Metabolites Reprogramming Induced by Spermine Contributing to Salt Tolerance in Creeping Bentgrass. Int. J. Mol. Sci. 23, 4472 (2022).

    Google Scholar 

  59. Bashir, K. et al. Ethanol-Mediated Novel Survival Strategy against Drought Stress in Plants. Plant Cell Physiol. 63, 1181–1192 (2022).

    Google Scholar 

  60. Nguyen, H. M. et al. Ethanol Enhances High-Salinity Stress Tolerance by Detoxifying Reactive Oxygen Species in Arabidopsis thaliana and Rice. Front. Plant Sci. 8, 1001 (2017).

    Google Scholar 

  61. Das, A. K. et al. Ethanol Treatment Enhances Physiological and Biochemical Responses to Mitigate Saline Toxicity in Soybean. Plants. 11, 272 (2022).

    Google Scholar 

  62. Rahman, M. M. et al. Ethanol Positively Modulates Photosynthetic Traits, Antioxidant Defense and Osmoprotectant Levels to Enhance Drought Acclimatization in Soybean. Antioxidants11, 516 (2022).

    Google Scholar 

  63. Bai, J., Jin, K., Qin, W., Wang, Y. & Yin, Q. Proteomic Responses to Alkali Stress in Oats and the Alleviatory Effects of Exogenous Spermine Application. Front. Plant Sci. 12, 627129 (2021).

    Google Scholar 

  64. Nahar, K. et al. Physiological and biochemical mechanisms of spermine-induced cadmium stress tolerance in mung bean (Vigna radiata L.) seedlings. Environ. Sci. Pollut. Res. 23, 21206–21218 (2016).

    Google Scholar 

  65. Li, Y. et al. Glycerol-Induced Powdery Mildew Resistance in Wheat by Regulating Plant Fatty Acid Metabolism, Plant Hormones Cross-Talk, and Pathogenesis-Related Genes. Int. J. Mol. Sci. 21, 673 (2020).

    Google Scholar 

  66. Raza, A. et al. Assessment of proline function in higher plants under extreme temperatures. Plant. Biol. 25, 379–395 (2023).

    Google Scholar 

  67. Heberle, H., Meirelles, G. V., da Silva, F. R., Telles, G. P. & Minghim, R. InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams. BMC Bioinformatics16, 169 (2015).

    Google Scholar 

  68. Guan, C. et al. Proline Biosynthesis Enzyme Genes Confer Salt Tolerance to Switchgrass (Panicum virgatum L.) in Cooperation With Polyamines Metabolism. Front. Plant Sci. 11, 46 (2020).

    Google Scholar 

  69. Hasan, M. M. et al. Spermine: Its Emerging Role in Regulating Drought Stress Responses in Plants. Cells10, 261 (2021).

    Google Scholar 

  70. Chowdhury, N. B. et al. A multi-organ maize metabolic model connects temperature stress with energy production and reducing power generation. iScience. 26, 108400 (2023).

    Google Scholar 

  71. Gorovits, R. et al. Interplay of stress responses to carbamazepine treatment, whitefly infestation and virus infection in tomato plants. Plant Stress. 1, 100009 (2021).

    Google Scholar 

  72. Mascellani, A. et al. Biochemical and physiological changes in Zea mays L. after exposure to the environmental pharmaceutical pollutant carbamazepine. Chemosphere329, 138689 (2023).

    Google Scholar 

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