Madurastatin B3, a rare aziridine derivative from actinomycete Nocardiopsis sp. LS150010 with potent anti-tuberculosis activity.
Since the discovery of the first antibiotic, natural products have played an important role in chemistry, biology and medicine. To explore the potential of bioactive compounds from microbes isolated from the southeast of Tibet, China, a crude extract library was constructed and screened against Staphylococcus aureus. The strain Nocardiopsis sp. LS150010 was scaled up and subjected to further chemical studies, resulting in the identification of N-salicyloyl-2-aminopropan-1,3-diol (2) and its rare aziridine derivative, madurastatin B3 (1). Their structures were determined by detailed analysis of 1D, 2D NMR and HRMS data. Compounds 1 and 2 displayed significant inhibitory activity against S. aureus and methicillin resistant S. aureus, with MIC values of 6.25 µg/mL. Compound 1 also showed potent inhibitory activity against Bacillus subtilis and Escherichia coli, as well as activity in a Mycobacterium tuberculosis Bacillus Calmette-Guérin infected THP-1 cell model.
Institute of Tibet Plateau Ecology, Agricultural and Animal Husbandry College, Tibet University, Linzhi, 860000, People's Republic of China.|National Forest Ecosystem Observation and Research Station of Tibet, Linzhi, 860000, People's Republic of China.
Xinjun
X
Zhang
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
Hongtao
H
He
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
Rong
R
Ma
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.|School of Biological Engineering, Tianjin University of Science and Technology, Tianjin, 300457, People's Republic of China.
Zengchun
Z
Ji
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.|College of Life Sciences, Hebei University, Baoding, 071002, People's Republic of China.
Qi
Q
Wei
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
Huanqin
H
Dai
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China. lzhang03@gmail.com.|State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China. lzhang03@gmail.com.
Lixin
L
Zhang
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China. songfuhang@im.ac.cn.
Fuhang
F
Song
D000192:Actinomycetales / Q000737:chemistry* / Q000145:classification / Q000302:isolation & purification; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology; D001388:Aziridines / Q000737:chemistry* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D002681:China; D004926:Escherichia coli / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D012988:Soil Microbiology
D000995:Antitubercular Agents; D001388:Aziridines; C033132:aziridine
Aziridine derivative; Bacillus Calmette-Guérin; Methicillin resistant Staphylococcus aureus; Nocardiopsis sp. LS150010