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

• DOI: 10.1021/acs.orglett.2c02879
• Publication Date: 2022-10-21T15:36:28Z
• Authors: Dongbo Xu; Jackie Metz; Dedra Harmody; Tara Peterson; Priscilla Winder; Esther A. Guzmán; Riccardo Russo; Peter J. McCarthy; Amy E. Wright; Guojun Wang
• Keywords: Methicillin-Resistant Staphylococcus aureus; 0301 basic medicine; Staphylococcus aureus; 03 medical and health sciences; Vancomycin Resistance; Microbial Sensitivity Tests; Sulfur; Anti-Bacterial Agents; 3. Good health

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.