The antimicrobial potential of marine fungal derived natural and semisynthetic butyrolactones analogues against MRSA

In our search for new antimicrobial agents from nature, the initial antimicrobial effect of the marine-derived fungus Aspergillus terreus strain 15F6 against Staphylococcus aureus and MRSA demonstrated promising effect. Large scale fermentation and bio-guided isolation led to the isolation of two natural butyrolactones (1 and 2). To study the structure activity relationship, we have prepared a few semisynthetic butyrolactone analogues with different substituents. Surprisingly, the semisynthetic analogue 1a demonstrated promising antimicrobial effect against MRSA but not S. aureus with MIC below 3 µM. Using in silico studies to unlock the potential mechanisms behind these observations, we have found that the new semisynthetic butyrolactone analogues successfully bind to the Mur-B binding site.