Shi Ting, Shao Chang-Lun, Liu Yang, Zhao Dong-Lin, Cao Fei, Fu Xiu-Mei, Yu Jia-Yin, Wu Jing-Shuai, Zhang Zhen-Kun, Wang Chang-Yun
Key Laboratory of Marine Drugs, the Ministry of Education of China, School of Medicine and Pharmacy, 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 Apr 3;11:572. doi: 10.3389/fmicb.2020.00572. eCollection 2020.
The soft coral-derived fungus (XS-20090075) was found to be a potential strain to produce substantial new compounds in our previous study. In order to explore its potential to produce more metabolites, chemical epigenetic manipulation was used on this fungus to wake its sleeping genes, leading to the significant changes of its secondary metabolites by using a histone deacetylase (HDAC) inhibitor. The most obvious difference was the original main products harziane diterpenoids were changed into cyclonerane sesquiterpenoids. Three new terpenoids were isolated from the fungal culture treated with 10 μM sodium butyrate, including cleistanthane diterpenoid, harzianolic acid A (), harziane diterpenoid, harzianone E (), and cyclonerane sesquiterpenoid, 3,7,11-trihydroxy-cycloneran (), together with 11 known sesquiterpenoids (-). The absolute configurations of - were determined by single-crystal X-ray diffraction, ECD and OR calculations, and biogenetic considerations. This was the first time to obtain cleistanthane diterpenoid and africane sesquiterpenoid from genus , and this was the first chlorinated cleistanthane diterpenoid. These results demonstrated that the chemical epigenetic manipulation should be an efficient technique for the discovery of new secondary metabolites from marine-derived fungi.
在我们之前的研究中，发现源自软珊瑚的真菌（XS - 20090075）是一种能够产生大量新化合物的潜在菌株。为了探索其产生更多代谢产物的潜力，对该真菌进行了化学表观遗传操作，以唤醒其沉睡的基因，通过使用组蛋白脱乙酰酶（HDAC）抑制剂导致其次级代谢产物发生显著变化。最明显的差异是原来的主要产物哈茨烷二萜类化合物转变为环戊烷倍半萜类化合物。从用10 μM丁酸钠处理的真菌培养物中分离出三种新的萜类化合物，包括克利斯坦烷二萜、哈茨醇酸A（）、哈茨烷二萜、哈茨酮E（）和环戊烷倍半萜、3,7,11 - 三羟基 - 环戊烷（），以及11种已知的倍半萜类化合物（ - ）。通过单晶X射线衍射、ECD和OR计算以及生源学考虑确定了 - 的绝对构型。这是首次从该属中获得克利斯坦烷二萜和阿非利加倍半萜，并且这是首个氯化克利斯坦烷二萜。这些结果表明，化学表观遗传操作应该是从海洋来源真菌中发现新的次级代谢产物的一种有效技术。
