An epigenetic modifier induces the production of new metabolites by Aspergillus terreus AST0006

The use of epigenetic modifiers to activate silent gene clusters of secondary metabolism in fungi has demonstrated to be an important strategy for producing novel metabolites [1],[2]. In this study, we investigated the use of histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), on the production of metabolites by Aspergillus terreus. In potato dextrose broth (PDB) medium, A. terreus produced (+)-terrein (1), (-)-6-hydroxymellein (2), (-)-6,7-dimethoxymellein (3), (-)-6-methoxymellein (4), and farnesol (5). Incorporation of SAHA into PDB culture medium of this fungus affected the metabolites pattern and produced two new 3-pyrone-coumarin metabolites 6 and 7 together with (+)-terrein (1), (-)-6-hydroxymellein (2), (-)-6,7-dimethoxymellein (3), (-)-6-methoxymellein (4), and farnesol (5). The identification of metabolites 1-5 was established by comparison of their spectroscopic data with those reported and the structures of new metabolites 6 and 7 were elucidated with the help of their 1D and 2D NMR and HRMS data. The absolute configurations of the new compounds were determined through the comparison of experimental and calculated ECD data.

These results support the use of epigenetic modifiers for obtaining new fungal secondary metabolites.

Fig. 1 Structures of compounds 1−7.

• References

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