Genome Mining for Mycemycin: Discovery and Elucidation of Related Methylation and Chlorination Biosynthetic Chemistries

A silent dibenzoxazepinone (DBP) biosynthetic gene cluster (myc) was mutagenically activated in Streptomyces olivaceus SCSIO T05, enabling the discovery of mycemycin C (4) and three new analogues [mycemycins F–H (1–3)]. Gene disruption, complementation experiments, and enzymatic assays unveiled salicylic acid and 5-Cl-kynurenine as biosynthetic precursors and shed significant functional insights into MycO, MycB, MycR, and MycJ, enzymes responsible for fine-tuning of the DBP scaffold