Talaromyces spp. are tunable producers of light-activated secondary metabolites with anticancer potential

Photodynamic therapy (PDT) is a promising treatment strategy for resistant or non-surgical tumors. To develop photosensitizers tailored to specific cancer types, new chemical scaffolds are needed. Macrofungi have recently been identified as a potent source of such compounds, particularly dimeric anthraquinones. However, the sources previously described (i.e., dermocyboid Cortinarii) cannot be cultivated in a biotechnologically applicable way. Thus, in this proof-of-concept study, we explored Talaromyces species (Ascomycota) for their potential to produce similar light-activated metabolites. Six species (T. islandicus, T. pinophilus, T. rotundus, T. ruber, T. stipitatus, and T. thailandensis) were selected and cultivated following a strict strain management protocol. Photobiological studies of their extracts lead to the identification of two new fungal photosensitizers that are structurally related to the fungal photosensitizer 7,7'-biphyscion. Subsequent cultivation experiments with changing conditions confirmed the potential to enhance production, turning T. islandicus into a promising microbial cell factory for the sustainable generation of novel photosensitizers.