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目的挖掘具有优良多重耐药菌(MDR)抗菌活性的次级代谢产物,为海洋新药研发提供分子多样性。方法对海洋芽孢杆菌B-9987进行大发酵,将发酵产物进行提取分离,每一步分离过程进行MDR活性追踪。结果 B-9987粗提物对4株MDR菌(金黄色葡萄球菌CCARM 3090、沙门氏菌CCARM 8250、大肠杆菌CCARM 1009、粪肠球菌CCARM 5203)具有良好的抗菌活性。通过HPLC分离纯化及MS、NMR等波谱分析获得了化合物1(Macrolactin F)和化合物2(Bacillaene A)。化合物1对MDR菌没有抗菌活性。由于化合物2对光、温度、氧气十分不稳定,无法直接测试活性。对含有化合物2的组分进行活性测试,确定了B-9987的MDR菌抗菌活性来自于Bacillaene类化合物。结论鉴定了B-9987中的抗MDR菌活性成分。
Objective To explore the secondary metabolites with antibacterial activity of multidrug-resistant bacteria (MDR) and to provide molecular diversity for R & D of marine drugs. Methods Large-scale fermentation of Bacillus subtilis B-9987 was carried out. The fermentation products were extracted and separated, and the MDR activity was traced in every step of the separation process. Results The crude extract of B-9987 had good antibacterial activity against four strains of MDR (Staphylococcus aureus CCARM 3090, Salmonella CCARM 8250, E. coli CCARM 1009 and Enterococcus faecalis CCARM 5203). The compounds 1 (Macrolactin F) and 2 (Bacillaene A) were obtained by HPLC separation and purification by MS and NMR. Compound 1 has no antibacterial activity against MDR bacteria. Since compound 2 is very unstable to light, temperature and oxygen, it is not possible to directly test the activity. The activity test of the components containing compound 2 confirmed that the antibacterial activity of B-9987 against MDR was from Bacillaene. Conclusion The anti-MDR bacteria active ingredient in B-9987 was identified.