Co-culture of <i>Aspergillus niger</i> IFM 59706 and RAW264 cells enhances the production of aurasperone A with nitric oxide inhibitory activity

Most actinomycetes and fungi have a multitude of silent biosynthetic genes whose activation could lead to the production of new natural products. Our group recently designed and used a co-culture method to isolate new natural products, based on the idea that pathogens might produce immune suppressors to avoid attack by immune cells. Here, we searched for compounds produced by the co-culture of immune cells with pathogenic fungi isolated from clinical specimens. The production of dimeric naphtho-γ-pyrone aurasperone A (1) was enhanced by the co-culture of pathogenic fungus Aspergillus niger IFM 59706 and RAW264 mouse macrophage-like cells. The absolute configuration of 1 was confirmed by comparison with the reported electronic circular dichroism spectrum. This is the first report of the inhibitory activity of 1 on nitric oxide production, an inflammatory mediator.