A Novel Anti-MDR Activity and In Silico Pharmacological Profiling of 2,4-Di-tertButylphenol from Indonesian Peat Soil Lysinibacillus sp. against DNA Gyrase

HistoryThe escalating global antimicrobial resistance (AMR) crisis drives the search for novel antibacterial compounds from underexplored sources.This study aimed to evaluate the broad-spectrum and anti-multi-drug resistant (MDR) activity of a Lysinibacillus isolate from Indonesian peat soil, identify its bioactive compound, and perform an in silico pharmacological profiling.Methods included antibacterial activity testing using the Kirby-Bauer disc diffusion assay against MDR and non-MDR pathogens, compound identification via Gas Chromatography-Mass Spectrometry (GC-MS), and prediction of ADMET properties, druglikeness, and molecular docking simulations against DNA gyrase subunit B using various in silico platforms.Results demonstrated that the Lysinibacillus sp.supernatant exhibited broad inhibitory activity, including against MRSA (inhibition zone of 16.16mm) and ESBL-producing E. coli (11.76mm).GC-MS analysis identified 2,4-Di-tert-butylphenol (2,4-DTBP) as the primary compound.In silico profiling revealed that 2,4-DTBP complied with all Lipinski's rules, possessed low toxicity (LD₅₀ 700mg/kg), a favourable pharmacokinetic profile (92% intestinal absorption, no inhibition of CYP450 enzymes), and strong binding affinity to DNA gyrase (-5.9kcal/mol).In conclusion, 2,4-DTBP from Lysinibacillus sp. is a promising antibacterial candidate, with a predicted mechanism of action via DNA gyrase inhibition, supported by an excellent in silico pharmacological profile for further development.