Chemistry and biosynthesis of bacterial polycyclic xanthone natural products

Covering: up to the end of 2021Bacterial polycyclic xanthone natural products (BPXNPs) are a growing family of natural xanthones featuring a pentangular architecture with various modifications to the tricyclic xanthone chromophore. Their structural diversities and various activities have fueled biosynthetic and chemical synthetic studies. Moreover, their more potent activities than the clinically used drugs make them potential candidates for the treatment of diseases. Future unraveling of structure activity relationships (SARs) will provide new options for the (bio)-synthesis of drug analogues with higher activities. This review summarizes the isolation, structural elucidation and biological activities and more importantly, the recent strategies for the microbial biosynthesis and chemical synthesis of BPXNPs. Regarding their biosynthesis, we discuss the recent progress in enzymes that synthesize tricyclic xanthone, the protein candidates for structural moieties (methylene dioxygen bridge and nitrogen heterocycle), tailoring enzymes for methylation and halogenation. The chemical synthesis part summarizes the recent methodology for the division synthesis and coupling construction of achiral molecular skeletons. Ultimately, perspectives on the biosynthetic study of BPXNPs are discussed.