Aspermerodione, a novel fungal metabolite with an unusual 2,6-dioxabicyclo[2.2.1]heptane skeleton, as an inhibitor of penicillin-binding protein 2a

Abstract

Rising drug resistance limits the treatment options infected by methicillin-resistant Staphylococcus aureus (MRSA). A promising solution for overcoming the resistance of MRSA is to inhibit the penicillin-binding protein 2a (PBP2a). A novel terpene-polyketide hybrid meroterpenoid, aspermerodione (1), characterized by an unusual 2,6-dioxabicyclo[2.2.1]heptane core skeleton, and a new heptacyclic analogue, andiconin C (2), were isolated and identified from the liquid cultures of endophytic fungus Aspergillus sp. TJ23. The structures and their absolute configurations of all chiral centers were elucidated via extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations and determined via single-crystal X-ray diffraction analysis. Aspemerodione (1) was found to be a potential inhibitor of PBP2a, and work synergistically with the β-lactam antibiotics oxacillin and piperacillin against MRSA.