Brominated and Sulfur-Containing Angucyclines Derived from a Single Pathway: Identification of Nocardiopsistins D-F.

One novel brominated nocardiopsistin D ( 1 ) and two new sulfur-containing nocardiopsistins E-F ( 2 - 3 ) were identified from Nocardiopsis sp. HB-J378. The biosynthetic gene cluster ncd featuring a brominase was identified. Compounds 1 - 3 exhibited significant anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activities with minimum inhibitory concentrations (MICs) of 0.098, 3.125, and 0.195 μg/mL, respectively. The single bromination in 1 drastically enhanced the anti-MRSA activity by 128-fold without altering cell toxicity and acquired new activities against the bacterial pathogens vancomycin-resistant S. aureus (VRSA), Enterococcus faecium , and Bacillus cereus .