Perylenequinones production induced by co-culturing Setophoma sp. and Penicillium brasilianum

Abstract Co-culture strategy can be applied to produce structural diversity of natural products. This approach also enables the understanding of the interaction mechanisms in microbial ecology. The present study aimed at the secondary metabolism diversification of the endophytic fungus Setophoma sp. by co-culturing it with Penicillium brasilianum and Talaromyces wortmannii, species also isolated as endophytes, and with Penicillium digitatum, a phytopathogenic fungus dangerous to Brazilian citriculture. The increase of perylenequinones (stemphyperylenol and derivatives) produced by Setophoma sp. strain was observed in the co-cultures in response to the endophytic P. brasilianum. The induced stemphyperylenol was isolated by combined chromatographic procedures and identified by spectroscopic techniques. Other perylenequinone derivatives were detected by UHPLC-DAD-HRMS based dereplication data analysis. Stemphyperylenol exhibited antifungal effects not only against P. brasilianum, but also against P. digitatum, the main postharvest pathogen of orange fruits, and Aspergillus fumigatus, an important human pathogenic fungus ubiquitous in soil. Preliminary insights concerning the mode of action of stemphyperylenol were determined by evaluating a collection of A. fumigatus mutants. Thus, stemphyperylenol may have the potential for agricultural applications, and it is also promising as a human antifungal compound. Moreover, the co-culture of an endophyte-endophyte system may represent a potential way to achieve the chemical diversity of bioactive molecules.