一株海洋链霉菌MMHS020的抗菌活性代谢产物

【背景】海洋微生物因其生存环境的多样性与独特性,已成为天然产物研究的重要来源。【目的】以一株太平洋海泥来源链霉菌MMHS020为出发菌株,筛选可促进其产生丰富代谢产物的发酵条件,挖掘菌株在抗菌抗肿瘤方面的潜力。【方法】采用单菌株多次级代谢产物策略对MMHS020菌株进行培养诱导,使其产生更丰富的活性代谢产物。双层平板法测定发酵产物对6种指示菌的抑菌活性。以硅胶柱层析、葡聚糖凝胶层析和制备层析等方法对代谢产物进行分离纯化,再通过质谱技术和~1H-NMR和~(13)C-NMR对化合物进行结构解析。【结果】链霉菌属MMHS020菌株可在较高浓度盐离子环境中产生丰富的抑菌活性代谢产物,显示出对枯草芽孢杆菌、结核分枝杆菌和藤黄微球菌等多种指示菌的抑制活性。从发酵产物中分离鉴定了3个化合物,分别是诺卡胺素(1)、麦角甾醇(2)和星形孢菌素(3)。其中星形孢菌素表现出白色念珠菌的抑制活性,而诺卡胺素则对其他几个指示菌表现出较强的抑制活性。【结论】海洋链霉菌MMHS020菌株可代谢产生丰富多样的生物活性物质,具有开发成为新型抑菌生物制剂的潜力。

Antibacterial secondary metabolites produced by marine Streptomyces sp. MMHS020

[Background] Marine microorganisms flourishing in diverse marine environments are widely recognized as rich sources of natural products. [Objective] Based on a Streptomyces sp. MMHS020 strain isolated from marine sediment, this study aimed to optimize fermentation conditions for abundant metabolites, and exploit the potential of the strain in antibacterial and antitumor activities. [Methods] Using a one strain-many compounds (OSMAC) approach, active metabolites were produced by strain MMHS020. Antibacterial activity for six indicator bacteria strains were traced using two-layer plate method. The metabolites were separated and purified by silica gel column chromatography, Sephadex column chromatography, and preparative chromatography. The compounds were elucidated by means of spectral analysis including ESI-MS, 1H-NMR, and 13C-NMR. [Results] Strain MMHS020 could produce diverse metabolites of antibacterial activity to inhibit the growth of all indicator bacteria such as Bacillus subtilis, Mycobacterium tuberculosis, and Micrococcus luteus when cultivated under high salt condition. Three compounds: nocardamine (1), ergosterol (2), and staurosporine (3) were isolated from the fermentation broth of strain MMHS020. Staurosporine was of inhibitory activity to Candida albicans, and nocardamine for the others. [Conclusion] Marine-derived Streptomyces sp. MMHS020, which produces a variety of bioactive metabolites, could be potentially developed as a novel antimicrobial agent.