Discovery of Cytotoxic Barbiturate-Bridged Dimeric Chrolactomycins from Catenulispora acidiphila TX15

Six new spirotetronate polyketides, chrolactomycins A-F (2-7), and the known chrolactomycin (1) were isolated and identified from Catenulispora acidiphila TX15. Chrolactomycins D-F (5-7) feature an unprecedented dimeric skeleton bridged by a rare barbiturate unit. Sequencing and characterization of a type I polyketide synthase biosynthetic gene cluster led to the proposal of a biosynthetic pathway for 1-7. Compounds 2-4 exhibited antibacterial activities, while 3-7 displayed cytotoxicity to multiple cancer cell lines, with dimer 5 demonstrating the most potent effects (IC50 = 2.2-7.7 μM).