Wu Jing-Shuai, Yao Guang-Shan, Shi Xiao-Hui, Rehman Saif Ur, Xu Ying, Fu Xiu-Mei, Zhang Xiu-Li, Liu Yang, Wang Chang-Yun
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, China.
Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
Front Microbiol. 2020 Jan 30;11:85. doi: 10.3389/fmicb.2020.00085. eCollection 2020.
Epigenetic agents, histone deacetylase inhibitor (SAHA) and DNA methyltransferase inhibitor (5-Aza), were added to Czapek-Dox medium to trigger the chemical diversity of marinederived fungus XS-20090066. By HPLC and H NMR analysis, the diversity of fungal secondary metabolites was significantly increased compared with the control. With the aid of MS/MS-based molecular networking, two new nucleoside derivatives, kipukasins K () and L () were obtained. Meanwhile, the yields of four known nucleoside derivatives were significantly enhanced. In addition, one new bisabolane sesquiterpene, aspergillusene E (), along with ten known derivatives were also isolated. The structures were elucidated by comprehensive spectroscopic methods of NMR and HRESIMS analysis. Compounds and displayed antibacterial activities against and with the MIC values of 8-16 μg/mL. Our study revealed that the fungus XS-20090066 has been effectively induced by chemical epigenetic manipulation with a combination of SAHA and 5-Aza to produce new metabolites.
将表观遗传试剂、组蛋白去乙酰化酶抑制剂（SAHA）和DNA甲基转移酶抑制剂（5-氮杂胞苷）添加到察氏培养基中，以激发海洋来源真菌XS-20090066的化学多样性。通过高效液相色谱（HPLC）和核磁共振氢谱（H NMR）分析，与对照相比，真菌次生代谢产物的多样性显著增加。借助基于串联质谱（MS/MS）的分子网络，获得了两种新的核苷衍生物，即基普卡辛K（）和L（）。同时，四种已知核苷衍生物的产量显著提高。此外，还分离出一种新的双环倍半萜，即曲霉烯E（）以及十种已知衍生物。通过核磁共振（NMR）和高分辨电喷雾电离质谱（HRESIMS）分析等综合光谱方法阐明了其结构。化合物和对和显示出抗菌活性，最低抑菌浓度（MIC）值为8-16μg/mL。我们的研究表明，SAHA和5-氮杂胞苷联合使用的化学表观遗传操作有效地诱导了真菌XS-20090066产生新的代谢产物。
