Zmijewski M J, Miller-Hatch K, Goebel M
Antimicrob Agents Chemother. 1982 May;21(5):787-93. doi: 10.1128/AAC.21.5.787.
Naphthyridinomycin is a novel quinone antibiotic that is produced in liquid shake cultures by Streptomyces lusitanus. Fermentation studies have shown that this antibiotic is produced maximally after 96 h of cell growth. L-[methyl-3H]methionine efficiently labels naphthyridinomycin when it is added to a fermentation mixture 24 h before culture is harvested. Unlabeled and radioactively labeled naphthyridinomycin were used to determine the mechanism of action of this unique antibiotic. Naphthyridinomycin inhibited bacterial growth primarily by inhibiting DNA synthesis. The structural similarity between naphthyridinomycin and the saframycins suggested that naphthyridinomycin might inhibit DNA synthesis by binding to the template. In vitro studies with radiolabeled naphthyridinomycin indicated that this antibiotic does specifically bind to calf thymus DNA. The binding reaction was enhanced by adding sulfhydryl-containing compounds; dithiothreitol was the best activating agent. DNA-naphthyridinomycin complexes were a poor substrate for enzymes that catalyze DNA-directed DNA and RNA syntheses. These results showed that naphthyridinomycin is similar to the saframycins in its reactivity toward DNA and suggested that the mechanism by which naphthyridinomycin inhibits DNA synthesis is through its ability to bind specifically to the DNA template of the cell.
萘啶霉素是一种新型醌类抗生素，由葡萄牙链霉菌在液体振荡培养中产生。发酵研究表明，这种抗生素在细胞生长96小时后产量最高。当在收获培养物前24小时将L-[甲基-³H]甲硫氨酸添加到发酵混合物中时，它能有效地标记萘啶霉素。使用未标记的和放射性标记的萘啶霉素来确定这种独特抗生素的作用机制。萘啶霉素主要通过抑制DNA合成来抑制细菌生长。萘啶霉素与沙弗霉素之间的结构相似性表明，萘啶霉素可能通过与模板结合来抑制DNA合成。用放射性标记的萘啶霉素进行的体外研究表明，这种抗生素确实能特异性地结合小牛胸腺DNA。通过添加含巯基的化合物可增强结合反应；二硫苏糖醇是最佳的活化剂。DNA-萘啶霉素复合物是催化DNA指导的DNA和RNA合成的酶的不良底物。这些结果表明，萘啶霉素在对DNA的反应性方面与沙弗霉素相似，并表明萘啶霉素抑制DNA合成的机制是通过其特异性结合细胞DNA模板的能力。
