The soft coral-derived fungus Trichoderma harzianum (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 (1), harziane diterpenoid, harzianone E (2), and cyclonerane sesquiterpenoid, 3,7,11-trihydroxy-cycloneran (3), together with 11 known sesquiterpenoids (4-14). The absolute configurations of 1-3 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 Trichoderma, 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.

中文翻译：

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由化学表观遗传操作诱导的来自珊瑚源真菌哈茨木霉 (XS-20090075) 的萜类化合物。

在我们之前的研究中，发现软珊瑚来源的真菌哈茨木霉 (XS-20090075) 是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，研究人员对这种真菌进行了化学表观遗传操作，以唤醒其休眠基因，通过使用组蛋白脱乙酰酶（HDAC）抑制剂，导致其次生代谢产物发生显着变化。最明显的区别是原来的主要产品哈齐烷二萜类化合物变成了环烯倍半萜类化合物。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 cleistanthan 二萜、harzianolic 酸 A (1)、harziane 二萜、harzianone E (2) 和 cyclonerane 倍半萜、3,7,11-三羟基-cycloneran ( 3)，以及 11 种已知的倍半萜类化合物 (4-14)。1-3的绝对构型通过单晶X射线衍射、ECD和OR计算以及生物遗传学考虑来确定。这是首次从木霉属中分离得到闭壳烷二萜和非洲倍半萜，也是第一个氯化闭壳烷二萜。这些结果表明化学表观遗传操作应该是从海洋衍生真菌中发现新的次生代谢物的有效技术。