Antibacterial Muraymycins from Mutant Strains of Streptomyces sp NRRL 30471

作者：Cui, Zheng; Wang, Xiachang; Koppermann, Stefan; Thorson, Jon S.; Ducho, Christian; Van Lanen, Steven G.^*

来源：Journal of Natural Products, 2018, 81(4): 942-948.

DOI：10.1021/acs.jnatprod.7b01054

• ACETYLMURAMYL-PENTAPEPTIDE-TRANSLOCASE
• CELL WALL SYNTHESIS
• PEPTIDE ANTIBIOTICS
• ESCHERICHIA-COLI
• LEAD STRUCTURES
• MRAY
• INHIBITION
• MUREIDOMYCIN
• ANALOGS
• SITE

Muraymycins are nucleoside antibiotics isolated from Streptomyces sp. NRRL 30471 and several mutant strains thereof that were generated by random, chemical mutagenesis. Reinvestigation of two mutant strains using new media conditions led to the isolation of three new muraymycin congeners, named B8, B9, and C6 (1-3), as well as a known muraymycin, Cl. Structures of the compounds were elucidated by HRMS and 1D and 2D NMR spectroscopic analyses. Complete 2D NMR assignments for the known muraymycin Cl are also provided for the first time. Compounds 1 and 2, which differ from other muraymycins by having an elongated, terminally branched fatty acid side chain, had picomolar IC50 values against Staphylococcus aureus and Aquifex aeolicus MraY and showed good antibacterial activity against S. aureus (MIC = 2 and 6 mu g/mL, respectively) and Escherichia coli Delta tolC (MIC = 4 and 2 mu g/mL, respectively). Compound 3, which is characterized by an N-acetyl modification of the primary amine of the dissacharide core that is shared among nearly all of the reported muraymycin congeners, greatly reduced its inhibitory and antibacterial activity compared to nonacylated muraymycin Cl, which possibly indicates this modification is used for self-resistance.

• 出版日期2018-4
• 单位南京中医药大学