Production of novel fungal secondary metabolites by epigenetically activating the silent biosynthetic gene clusters.

在本研究中，我们发现了利用HADC和DNA甲基转移酶抑制剂等表观遗传修饰因子激活真菌次生代谢的有效条件。在此条件下，我们成功地从隐生生物合成途径中分离出结构多样的新型真菌次生代谢物，显示了扩大天然产物组成的化学空间的实用性。此外，我们还获得证据表明，真菌中表观遗传酶LaeA的过表达可能是促进其次生代谢产物产生的一种途径。

In this study, we found some effective conditions for activating fungal secondary metabolism by using epigenetic modifiers such as HADC and DNA methyltransferase inhibitors. Using the conditions, we successfully isolated structurally diverse novel fungal secondary metabolites from cryptic biosynthetic pathways, showing the utility to enlarge chemical space composed of natural products. In addition, we obtained the evidence that over expression of LaeA, an epigenetic enzyme, in fungi is possible way to enhance their production of secondary metabolites.