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

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

doi:10.3389/fmicb.2020.00085

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

Front Microbiol. 2020 Jan 30:11:85. doi: 10.3389/fmicb.2020.00085. eCollection 2020.

Authors

Jing-Shuai Wu^{1

2}, Guang-Shan Yao^{1

2

3}, Xiao-Hui Shi^{1

2}, Saif Ur Rehman^{1

2}, Ying Xu⁴, Xiu-Mei Fu^{1

2}, Xiu-Li Zhang^{1

2}, Yang Liu⁵, Chang-Yun Wang^{1

2}

Affiliations

¹ Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, China.
² Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
³ Institute of Oceanography, Minjiang University, Fuzhou, China.
⁴ Shenzhen Key Laboratory of Marine Bioresource and Eco-Environmental Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.
⁵ Institute for Insect Biotechnology, Justus Liebig University Giessen, Giessen, Germany.

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 ¹H 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.

Keywords: Aspergillus versicolor; DNA methyltransferase inhibitor; antibacterial activities; antifouling activities; bisabolane sesquiterpenes; histone deacetylase inhibitor; nucleoside derivatives.