第十五届海洋药物学术年会暨2021国际海洋药物研讨会

47 / 2021-10-09 23:19:07

Activation of Secondary Metabolite Biosynthesis by Deleting the Histone Deacetylase in the Marine-derived Fungus Aspergillus terreus

Aspergillus terreus,histone deacetylase,deletion,secondary metabolite

Aspergillus terreus is well-known for its ability of biosynthesis of valuable pharmaceuticals, as well as structurally unique natural products. Although a number of secondary metabolites with novel structures have been discovered in A. terreus,^[1-3] numerous promising cryptic secondary metabolites remain to be mined. Therefore, its outstanding metabolic potentials deserve to be further explored. In our study, to further explore the secondary metabolite potential of a marine-derived A. terreus, the essential histone deacetylase gene was deleted. After scaled fermentation and isolation, a pair of new azaphilones (compounds 1 and 2) were obtained. Their planar structures and absolute configurations were elucidated by using of HRESIMS, NMR spectroscopy and electronic circular dichroism spectra. These two compounds displayed antifungal activities against Candida with the MIC values ranging from 18.0-47.9 μM. Compound 1 exhibited moderate cytotoxic activity against human breast cancer cell line MDA-MB-231. This study provides novel evidences that the histone deacetylase gene plays essential and global roles in repressing the expression of genes associated with secondary metabolites in fungi, and its deletion represents an efficient strategy to tap new products in A. terreus.