Genomics-Inspired Discovery of Three Antibacterial Active Metabolites, Aurantinins B, C, and D from Compost-Associated Bacillus subtilis fmb60.
Fmb60 is a wild-type Bacillus subtilis isolated from compost with significant broad-spectrum antimicrobial activities. Two novel PKS clusters were recognized in the genome sequence of fmb60, and then three polyene antibiotics, aurantinins B, C, and D, 1-3, were obtained by bioactivity-guided isolation from the fermentation of fmb60. The structures of aurantinins B-D were elucidated by LC-HRMS and NMR data analysis. Aurantinins C and D were identified as new antimicrobial compounds. The three aurantinins showed significant activity against multidrug-resistant Staphylococcus aureus and Clostridium sporogenes. However, aurantinins B-D did not exhibit any cytotoxicity (IC50 > 100 μg/mL) against LO2 and Caco2 cell lines by MTT assay. Furthermore, using S. aureus as a model bacterium to explore the antibacterial mechanism of aurantinins B-D, it was revealed that the bactericidal activity of aurantinins B-D was related to their ability to disrupt the cell membrane.
College of Food Science and Technology, Nanjing Agricultural University , 1 Weigang, Nanjing 210095, China.
Jie
J
Yang
College of Food Science and Technology, Nanjing Agricultural University , 1 Weigang, Nanjing 210095, China.
Xiaoyu
X
Zhu
College of Food Science and Technology, Nanjing Agricultural University , 1 Weigang, Nanjing 210095, China.
Mingming
M
Cao
College of Food Science and Technology, Nanjing Agricultural University , 1 Weigang, Nanjing 210095, China.
Changbao
C
Wang
College of Food Science and Technology, Nanjing Agricultural University , 1 Weigang, Nanjing 210095, China.
Chong
C
Zhang
College of Food Science and Technology, Nanjing Agricultural University , 1 Weigang, Nanjing 210095, China.
Zhaoxin
Z
Lu
College of Food Science and Technology, Nanjing Agricultural University , 1 Weigang, Nanjing 210095, China.
Fengxia
F
Lu
D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001412:Bacillus subtilis / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D003013:Clostridium / Q000187:drug effects; D023281:Genomics; D008826:Microbial Sensitivity Tests; D011090:Polyenes / Q000378:metabolism / Q000494:pharmacology*; D012988:Soil Microbiology; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D011090:Polyenes; C000619719:aurantinin C; C000619720:aurantinin D; C055559:aurantinin B
Bacillus subtilis; aurantinins; bacteria control; genome mining; noncytotoxicity; polyketide synthase