Discovery of Antibacterial Tetracycline-Type Natural Products Misiomycins E–H through KASIII Genome Mining and Regulator Overexpression

Guided by KASIII genome mining in combination with an in situ gene cluster activation strategy, we discovered a series of tetracycline natural products featuring atypical starter units, misiomycins E–H (1–4, respectively), from Streptomyces misionensis CGMCC 4.1982. The structures were determined by HR-ESI-MS, 1D and 2D NMR spectroscopy, MS/MS fragmentation, and genomic data. Misiomycins G and H demonstrated potent antibacterial activity against Staphylococcus aureus, with minimum inhibitory concentrations (MICs) of 3.74 and 7.03 μg/mL, respectively.