On April 21, 2016, Prof. Delin You’s Group published a research article entitled "A multifunctional monooxygenase XanO4 catalyzes xanthone formation in xantholipin biosynthesis via a cryptic demethoxylation" in Cell Chemical Biology as an "Issue Highlights" in the journal.
Xantholipin and several related polycyclic xanthone antibiotics feature a unique xanthone ring nucleus within a highly oxygenated, angular fused hexacyclic system. In this study, Prof. Delin You’s Group demonstrated that a flavin-dependent monooxygenase (FMO) XanO4 catalyzes the oxidative transformation of an anthraquinone to a xanthone system during the biosynthesis of xantholipin. In vitro isotopic labeling experiments showed that the reaction involves sequential insertion of two oxygen atoms, accompanied by an unexpected cryptic demethoxylation reaction. Moreover, characterizations of homologous FMOs of XanO4 suggested the generality of XanO4-like-mediated reaction for the assembly of xanthone ring in the biosynthesis of polycyclic xanthone antibiotics. These findings not only expand the repertoire of FMOs activities, but also reveal a novel mechanism for xanthone ring formation.
PhD students Lingxin Kong is the first author of this article. This research was supported by grants from the National Science Foundation of China, the Ministry of Science and Technology, Shanghai Pujiang Program from the Shanghai Municipal Council of Science and Technology.