Antibacterial Activity and Molecular Docking of a Bicyclic Lactone as aBiotransformed Product from β-caryophyllene using Aspergillus niger

introduction: β-caryophyllene and its derivatives play an important role as antibacterial agents. This study is a continuation of the biotransformation of β-caryophyllene using Aspergillus niger, where metabolite 1 was isolated and identified in our previous study. Here, we investigate its antibacterial activity against both Gram-positive and Gram-negative bacteria, in addition to molecular docking studies. methods: The antibacterial activity of the transformed product was evaluated by using the standard agar cup bioassay method. A deep computational study has been performed to elucidate the antibacterial mechanism of Compound 1, including Glide XP docking and Prime/MMGBSA free-energy calculations against PBP1b, DNA gyrase AⁿBⁿ, and ClpP. results: Metabolite 1 showed significant growth inhibitions of Gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus (9.0 ± 0.2 mm and 10.0 ± 0.2 mm). Also, against Gramnegative bacteria, Pseudomonas aeruginosa, Escherichia coli, and Salmonella typhi (7.0 ± 0.2 mm, 8.0 ± 0.2 mm, and 9.0 ± 0.2 mm). ADMET analysis indicated that Compound 1 has excellent oral absorption (83.3%) and fully complies with Lipinski’s rules, outperforming imipenem. discussion: The present study aimed to evaluate antibacterial activities of metabolite 1 (100 ug/mL) against Gram-positive organisms (B. subtilis and S. aureus) and Gram-negative organisms (P. aeruginosa, E. coli, and S. typhi), in comparison with imipenem, followed by computational studies. conclusion: Metabolite 1 showed significant antibacterial activities against Gram-positive and Gram-negative organisms. Our findings demonstrate that Compound 1 binds strongly to ClpP (Glide Gscore –6.27; ΔG_bind –34.51 kcal/mol), engaging key hydrogen-bond and hydrophobic interactions, thus reinforcing its promise as a multi-target antibacterial candidate