Dashti Yousef, Grkovic Tanja, Abdelmohsen Usama Ramadan, Hentschel Ute, Quinn Ronald J
Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.
Department of Botany II, Julius-von-Sachs Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs-Platz 3, D-97082 Würzburg, Germany.
Mar Drugs. 2014 May 22;12(5):3046-59. doi: 10.3390/md12053046.
Two sponge-derived actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163, were grown in co-culture and the presence of induced metabolites monitored by ¹H NMR. Ten known compounds, including angucycline, diketopiperazine and β-carboline derivatives 1-10, were isolated from the EtOAc extracts of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163. Co-cultivation of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163 induced the biosynthesis of three natural products that were not detected in the single culture of either microorganism, namely N-(2-hydroxyphenyl)-acetamide (11), 1,6-dihydroxyphenazine (12) and 5a,6,11a,12-tetrahydro-5a,11a-dimethyl[1,4]benzoxazino[3,2-b][1,4]benzoxazine (13a). When tested for biological activity against a range of bacteria and parasites, only the phenazine 12 was active against Bacillus sp. P25, Trypanosoma brucei and interestingly, against Actinokineospora sp. EG49. These findings highlight the co-cultivation approach as an effective strategy to access the bioactive secondary metabolites hidden in the genomes of marine actinomycetes.
两种源自海绵的放线菌，即动孢放线菌属（Actinokineospora sp.）EG49和诺卡氏放线菌属（Nocardiopsis sp.）RV163，进行共培养，并通过¹H NMR监测诱导代谢产物的存在。从动孢放线菌属EG49和诺卡氏放线菌属RV163的乙酸乙酯提取物中分离出10种已知化合物，包括安古环素、二酮哌嗪和β-咔啉衍生物1 - 10。动孢放线菌属EG49和诺卡氏放线菌属RV163的共培养诱导了三种天然产物的生物合成，这三种天然产物在任何一种微生物的单培养中均未检测到，即N-(2-羟基苯基)-乙酰胺（11）、1,6-二羟基吩嗪（(12）和5a,6,11a,12-四氢-5a,11a-二甲基[1,4]苯并恶嗪并[3,2-b][1,4]苯并恶嗪（13a）。当测试其对一系列细菌和寄生虫的生物活性时，只有吩嗪12对芽孢杆菌属P25、布氏锥虫有活性，有趣的是，对动孢放线菌属EG49也有活性。这些发现突出了共培养方法作为一种有效策略，可用于获取隐藏在海洋放线菌基因组中的生物活性次生代谢产物。
