Diasperonins A-F: Anti-inflammatory Aspertetronin Dimers Discovered via BBMN and Heterologous Expression Strategy

By integrating heterologous expression of the entire biosynthetic gene cluster in Aspergillus nidulans and a building blocks-based molecular networking (BBMN) strategy, six novel aspertetronin dimers (diasperonins A-F, 1-6) with three unprecedented skeletons and two additional novel congeners (7-8) were characterized from the engineered strain. High monomer levels from gene cluster overexpression likely triggered nonenzymatic dimerization. Compound 7 suppressed the NF-κB pathway in LPS-induced RAW264.7 cells and mouse model, demonstrating potent anti-inflammatory activity.