(+)-Skyrin

(+)-Skyrin is a fungal bisanthraquinone originally characterized as a metabolite accompanying rugulosin from Penicillium rugulosum. Biosynthetic studies established that skyrin forms via 5,5'-oxidative dimerization of emodin radicals catalyzed by the cytochrome P450 monooxygenase RugG within the rug gene cluster, defining the molecular basis for bisanthraquinone assembly. Skyrin has been proposed as a precursor in hypericin biosynthesis and is localized in Hypericum species leaves as shown by MALDI-HRMS imaging. Functional studies demonstrated that skyrin lacks intrinsic genotoxicity, exhibits moderate DNA-protective effects, and shows selective cytotoxicity toward HepG2 cancer cells compared with non-cancerous human lymphocytes. These findings define skyrin as a biosynthetically characterized fungal polyketide dimer with distinct polyphenolic bioactivity.