Harnessing L-asparaginase from Solanaceae plants: Purification and molecular dynamics studies for cancer targeting

Abstract. Aisha A, Sajjad A, Munawar N, Azam HMH, Ishtiaq U, Nawaz S. 2025. Harnessing L-asparaginase from Solanaceae plants: Purification and molecular dynamics studies for cancer targeting. Asian J Nat Prod Biochem 23: 27-37. Conventional chemotherapeutic regimens have their adverse effects. Our research, however, offers a potential breakthrough in cancer treatment. We have discovered that l-asparaginase from plant sources can selectively target L-asparagine, the nutritional requirement of cancer cells. The aim was to elucidate the function and mechanism of action of anticancer and bactericidal plant-sourced L-asparaginase protein via proteomics. Biochemical, chromatographic techniques and SDS PAGE were employed for purifying L-asparaginase from Solanaceae plants, including Datura innoxia, Atropa belladonna, Hyoscyamus niger (leaves), Lycopersicum esculentum (fruit), Solanum tuberosum (roots), and Ipomoea batatas (roots). Michaelis-Menten and Lineweaver Burk's plot demonstrated the characterization of the extracted protein from D. innoxia, which exhibited the maximum enzyme activity. Further, molecular dynamics simulations were employed to establish antimicrobial efficiency (through potato disc assays) and to determine the antitumor efficiency. Kinetic studies of L-asparaginase from D. innoxia revealed optimal activity at pH 8-8.5 and 37°C with [S]=8 ?g/mL, Km 0.1766 ?mol provided 1/2V max 0.525 ?mol/min, while the protein band of approximately 30 kDa. Ethanolic extracts inhibited growth 54.5, 33.30, and 45.65% among Escherichia coli, Staphylococcus aureus, and Bacillus subtilis, respectively, with MIC 6.25 mg/dL. L-asparaginase anticancer mediation was validated using molecular dynamics simulations (InterPro Scan), identifying novel domain IPR027474 and active sites IPR020827 and IPR027475. This mechanism provided insights into anticancer action and potential sources for combinational therapies in clinical oncology.