Antimicrobial Potential, Mechanisms, and Biosynthesis Pathways of Lichen-Derived Bioactive Compounds; A Systematic Review

Abstract

Lichens, symbiotic organisms comprising fungi and photosynthetic partners, have gained particular attention due to their rich nutritional profile, which includes significant bioactive compounds with strong antimicrobial potential. This review collectively highlights the antimicrobial activity, its mechanism of action, and synthesis of lichen-derived compounds, advocating for their effective use as novel agents against microbial infections. Lichen metabolites, especially usnic acid and atranorin, exhibited significant activity against various multidrug-resistant bacterial strains and also antifungal activity, especially against Candida albicans and Aspergillus species. Their mechanism of action against infectious microbes involves cell wall and cell membrane formation inhibition, RNA/DNA synthesis disruption, and efflux pump inhibition. Recent advanced genomic and metabolomics studies have explored the biosynthesis pathways of these bioactive compounds with the involvement of several key enzymes, especially polyketide synthases (PKSs), and genes such as biosynthetic gene clusters (BGCs). Despite significant studies, there remain gaps in evaluating the pharmacogenomics, toxicity, and in vivo efficiency of these bioactive compounds. However, there is also a need for further study on sustainable enhanced extraction techniques and nano-encapsulation for improved and enhanced availability. This review synthesizes evidence that lichen compounds target microbial cell structures, nucleic acid synthesis, and efflux pumps, with emerging potential for drug development, also urges for advanced approaches such as nano-encapsulation and AI-driven drug discovery to utilize their complete potential.