Epigenetic Agents Trigger the Production of Bioactive Nucleoside Derivatives and Bisabolane Sesquiterpenes From the Marine-Derived Fungus Aspergillus versicolor

Abstract

Epigenetic agents, histone deacetylase inhibitor (SAHA) and DNA methyltransferase inhibitor (5-Aza), were added to Czapek-Dox medium to trigger the chemical diversity of marine-derived fungus Aspergillus versicolor XS-20090066. By HPLC and 1 H NMR analysis, the diversity of fungal secondary metabolites was significantly increased compared with the control. With the aid of MS/MS-based molecular networking, two new nucleoside derivatives, kipukasins K (1) and L (2) were obtained. Meanwhile, the yields of four known nucleoside derivatives were significantly enhanced. In addition, one new bisabolane sesquiterpene, aspergillusene E (7), along with ten known derivatives were also isolated. The structures were elucidated by comprehensive spectroscopic methods of NMR and HRESIMS analysis. Compounds 1 and 7 displayed antibacterial activities against Staphylococcus epidermidis and Staphylococcus aureus with the MIC values of 8-16 µg/mL. Our study revealed that the fungus A. versicolor XS-20090066 has been effectively induced by chemical epigenetic manipulation with a combination of SAHA and 5-Aza to produce new metabolites.

Terpenoids From the Coral-Derived Fungus Trichoderma harzianum (XS-20090075) Induced by Chemical Epigenetic Manipulation

“…During our ongoing investigation to discover bioactive marine natural products, we have also obtained new metabolites from marine-derived fungi by using chemical epigenetic modification (Zhang et al, 2014;Chen et al, 2016;Wu et al, 2019Wu et al, , 2020. In our previous work, a series of harziane diterpenoids and hydroxyanthraquinones have been discovered from the fungus T. harzianum (XS-20090075) isolated from a soft coral collected from the South China Sea (Shi et al, 2018;Zhao et al, 2019).…”

Sorbicillinoid Derivatives From Sponge-Derived Fungus Trichoderma reesei (HN-2016-018)

“…All samples were dissolved in DMSO. The adriamycin was used as a positive control and DMSO was used as a negative control (Wu et al, 2020).…”

Benzyl Furanones and Pyrones from the Marine-Derived Fungus Aspergillus terreus Induced by Chemical Epigenetic Modification

“…In recent years, during our efforts to explore new bioactive marine natural products [ 9 ], chemical epigenetic manipulation has been applied to marine-derived fungi to mine their potential ability to produce metabolic products [ 9 , 10 , 11 , 12 , 13 , 14 ]. In our previous work, a series of thiodiketopiperazines and 3,4-dihydroisocoumarin derivatives were isolated from the starch liquid culture of A. terreus RA2905 derived from sea hare Aplysia pulmonica [ 15 ].…”