AUTHOR=Wu Jing-Shuai , Yao Guang-Shan , Shi Xiao-Hui , Rehman Saif Ur , Xu Ying , Fu Xiu-Mei , Zhang Xiu-Li , Liu Yang , Wang Chang-Yun 

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

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00085

DOI=10.3389/fmicb.2020.00085

ISSN=1664-302X

ABSTRACT=<p>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<italic>-</italic>derived fungus <italic>Aspergillus versicolor</italic> XS-20090066. By HPLC and <sup>1</sup>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 (<bold>1</bold>) and L (<bold>2</bold>) were obtained. Meanwhile, the yields of four known nucleoside derivatives were significantly enhanced. In addition, one new bisabolane sesquiterpene, aspergillusene E (<bold>7</bold>), along with ten known derivatives were also isolated. The structures were elucidated by comprehensive spectroscopic methods of NMR and HRESIMS analysis. Compounds <bold>1</bold> and <bold>7</bold> displayed antibacterial activities against <italic>Staphylococcus epidermidis</italic> and <italic>Staphylococcus aureus</italic> with the MIC values of 8–16 μg/mL. Our study revealed that the fungus <italic>A. versicolor</italic> XS-20090066 has been effectively induced by chemical epigenetic manipulation with a combination of SAHA and 5-Aza to produce new metabolites.</p>