Karakterisasi Senyawa Berdasarkan Pendekatan Metabolomik dan Aktivitas Antibakteri dengan Staphylococcus aureus pada Liken dari Kawasan Jampit, Bondowoso

Abstract

The increasing prevalence of antibacterial resistance, particularly in Staphylococcus aureus, has become a major global health concern, highlighting the urgent need to discover novel antibacterial agents from natural resources. Lichens are symbiotic organisms known to produce diverse secondary metabolites with promising pharmacological properties; however, comprehensive metabolomic characterization of Indonesian lichens remains limited. This study aimed to characterize the metabolite profiles of methanol fractions obtained from lichens collected in the Jampit highlands, Bondowoso, evaluate their antibacterial activity against Staphylococcus aureus, investigate the relationship between metabolite profiles and antibacterial activity using a metabolomics approach, and characterize the putative bioactive compound responsible for the observed activity. Nine lichen species were extracted with methanol and fractionated using n-hexane. Metabolite profiling was performed using High-Performance Liquid Chromatography (HPLC), while antibacterial activity was evaluated by a single-concentration broth microdilution assay. Chromatographic and antibacterial datasets were integrated through Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) to identify metabolites associated with antibacterial activity. The candidate compound was subsequently characterized by High-Resolution Mass Spectrometry (HRMS), followed by in silico validation through molecular docking against three essential S. aureus target proteins (1QXY, 3SQY, and 3U2D) and pharmacokinetic prediction using SwissADME. The results demonstrated substantial interspecies variation in metabolite composition and antibacterial activity. Chemometric analysis successfully identified metabolites contributing to antibacterial activity, while HRMS characterization and molecular docking supported the potential of a candidate compound as an antibacterial agent against Staphylococcus aureus. These findings provide a preliminary scientific basis for the discovery of lichen-derived antibacterial compounds and support further isolation, structural elucidation, and biological validation toward the development of natural product-based antibacterial agents.