TY - JOUR
T1 - 8-deoxy-rifamycin derivatives from amycolatopsis mediterranei S699 ∆rift strain
AU - Ye, Feng
AU - Shi, Yanrong
AU - Zhao, Shengliang
AU - Li, Zhiying
AU - Wang, Haoxin
AU - Lu, Chunhua
AU - Shen, Yuemao
N1 - Funding Information:
Funding: This work was supported by the National Key Research and Development Program (2019YFA0905402), the National Natural Science Foundation of China (81673317, 81602979, 81530091,) the Program for Changjiang Scholars and Innovative Research Team in University (IRT_17R68), and the Open Funding Project of State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University (MMLKF17-09).
PY - 2020/9
Y1 - 2020/9
N2 - Proansamycin X, a hypothetical earliest macrocyclic precursor in the biosynthesis of rifamycin, had never been isolated and identified. According to bioinformatics analysis, it was proposed that RifT (a putative NADH-dependent dehydrogenase) may be a candidate target responsible for the dehydrogenation of proansamycin X. In this study, the mutant strain Amycolatopsis mediterranei S699 ∆rifT was constructed by deleting the rifT gene. From this strain, eleven 8-deoxy-rifamycin derivatives (1–11) and seven known analogues (12–18) were isolated. Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and high-resolution ESI mass spectra. Compound 1 is a novel amide N-glycoside of seco-rifamycin. Compounds 2 and 3 feature conserved 11,12-seco-rifamycin W skeleton. The diverse post-modifications in the polyketide chain led to the production of 4–11. Compounds 2, 3, 5, 6, 13 and 15 exhibited antibacterial activity against Staphylococcus aureus (MIC (minimal inhibitory concentration) values of 10, 20, 20, 20, 40 and 20 µg/mL, respectively). Compounds 14, 15, 16, 17 and 18 showed potent antiproliferative activity against KG1 cells with IC50 (half maximal inhibitory concentration) values of 14.91, 44.78, 2.16, 18.67 and 8.07 µM, respectively.
AB - Proansamycin X, a hypothetical earliest macrocyclic precursor in the biosynthesis of rifamycin, had never been isolated and identified. According to bioinformatics analysis, it was proposed that RifT (a putative NADH-dependent dehydrogenase) may be a candidate target responsible for the dehydrogenation of proansamycin X. In this study, the mutant strain Amycolatopsis mediterranei S699 ∆rifT was constructed by deleting the rifT gene. From this strain, eleven 8-deoxy-rifamycin derivatives (1–11) and seven known analogues (12–18) were isolated. Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and high-resolution ESI mass spectra. Compound 1 is a novel amide N-glycoside of seco-rifamycin. Compounds 2 and 3 feature conserved 11,12-seco-rifamycin W skeleton. The diverse post-modifications in the polyketide chain led to the production of 4–11. Compounds 2, 3, 5, 6, 13 and 15 exhibited antibacterial activity against Staphylococcus aureus (MIC (minimal inhibitory concentration) values of 10, 20, 20, 20, 40 and 20 µg/mL, respectively). Compounds 14, 15, 16, 17 and 18 showed potent antiproliferative activity against KG1 cells with IC50 (half maximal inhibitory concentration) values of 14.91, 44.78, 2.16, 18.67 and 8.07 µM, respectively.
KW - Amycolatopsis mediterranei S699
KW - Dehydrogenation
KW - N-glycoside rifamycin
KW - Proansamycin X
KW - Rifamycin
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U2 - 10.3390/biom10091265
DO - 10.3390/biom10091265
M3 - Article
C2 - 32887371
AN - SCOPUS:85090505765
VL - 10
SP - 1
EP - 14
JO - Biomolecules
JF - Biomolecules
SN - 2218-273X
IS - 9
M1 - 1265
ER -