Broad-spectrum antibacterial activity of a bioactive fraction containing laucysteinamide A-like metabolite from the soil crust cyanobacterium Desmonostoc sp.

UNLABELLED: Antimicrobial resistance has become a growing global concern, and there is an urgent need for novel antibiotics. Many Cyanobacterial strains produce important biologically active secondary metabolites, including antimicrobial compounds. In this study, Desmonostoc sp., a Nostocalean cyanobacterium identified using polyphasic approaches, was investigated for antimicrobial metabolites, leading to the isolation of a fraction containing laucysteinamide A (LcA)-like metabolite. A bioassay-guided fractionation method was employed to extract and purify this compound using various chromatography techniques, including HPLC. The bioactive fraction was examined by FT-IR, ESI-MS, HR-MS, LC-MS/MS, and ¹H NMR spectroscopy. The fraction shows moderate antibacterial activity against five pathogenic bacteria, and the MIC values were found to be 12.5 [Formula: see text]ml against B. subtilis MTCC 121, E. coli MTCC 1667, S. typhimurium MTCC 98, L. monocytogenes MTCC 657, and 6.25 [Formula: see text]ml against S. aureus MTCC 96. Molecular docking and MD simulation study revealed the strong and stable binding affinities of LcA against Dihydrofolate reductase enzyme, a well-established antibiotic target, by interfering with its NADP binding site, and binding affinity was found to be -9.29 kcal/mol for E. coli, - 6.86 kcal/mol for B. subtilis, - 6.64 kcal/mol for S. typhimurium,  7.24 kcal/mol for L. monocytogenes, and - 8.20 kcal/mol for S. aureus, respectively. The ADMET predictions suggest that LcA is a promising drug candidate due to its compliance with Lipinski's Rule of Five, a good bioavailability score, and favorable pharmacokinetic features. The findings underscore the therapeutic potential of the bioactive fraction as an effective antibacterial agent, providing valuable insights for future drug development.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-026-04996-5.