We screened for bacterial phospho-N-acetylmuramyl-pentapeptide-translocase (MraY: EC 126.96.36.199) inhibitors with the aim of discovering novel antibiotics and observed inhibitory activity in the culture broth of an actinomycete, SANK 60501. The active compounds, muraminomicins A, B, C, D, E1, E2, F, G, H, and I exhibited strong inhibitory activity against MraY with IC50 values of 0.0105, 0.0068, 0.0104, 0.0099, 0.0115, 0.0109, 0.0089, 0.0134, 0.0186, and 0.0094 μg ml−1, respectively. Although muraminomicin F exhibited favorable antibacterial activity against drug-resistant Gram-positive bacteria, this activity was reduced with the addition of serum. To efficiently supply the core component for chemical modification studies, production was carried out in a controlled trial by adding myristic acid to the medium, and a purification method suitable for large-scale production was successfully developed.
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Dedicated with respect to Professor K. Isono’s long-standing and outstanding contribution to the isolation, structural determination, and mechanism of action of natural products, particularly nucleic acid antibiotics.
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Fujita, Y., Kagoshima, Y., Masuda, T. et al. Muraminomicins, new lipo-nucleoside antibiotics from Streptosporangium sp. SANK 60501-structure elucidations of muraminomicins and supply of the core component for derivatization. J Antibiot 72, 943–955 (2019) doi:10.1038/s41429-019-0215-7
Liposidomycin, the first reported nucleoside antibiotic inhibitor of peptidoglycan biosynthesis translocase I: The discovery of liposidomycin and related compounds with a perspective on their application to new antibiotics
The Journal of Antibiotics (2019)
The Journal of Antibiotics (2019)