Eremophilane Sesquiterpenes from a Deep Marine-Derived Fungus, Aspergillus sp. SCSIOW2, Cultivated in the Presence of Epigenetic Modifying Agents.
Chemical epigenetic manipulation was applied to a deep marine-derived fungus, Aspergillus sp. SCSIOW2, resulting in significant changes of the secondary metabolites. Three new eremophilane-type sesquiterpenes, dihydrobipolaroxin B (2), dihydrobipolaroxin C (3), and dihydrobipolaroxin D (4), along with one known analogue, dihydrobipolaroxin (1), were isolated from the culture treated with a combination of histone deacetylase inhibitor (suberohydroxamic acid) and DNA methyltransferase inhibitor (5-azacytidine). 1-4 were not produced in the untreated cultures. 2 and 3 might be artificial because 1 could form 2 and 3 spontaneously in water by intracellular acetalization reaction. The absolute configurations of 1 and 2 were assigned based on ECD spectroscopy combined with time-dependent density functional theory calculations. All four compounds exhibited moderate nitric oxide inhibitory activities without cytotoxic effects.
Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. lwang@szu.edu.cn.
Liyan
L
Wang
Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. lmengjie16@163.com.
Mengjie
M
Li
Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. tangjianqiang888@163.com.
Jianqiang
J
Tang
Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. lixiaof@szu.edu.cn.
Xiaofan
X
Li
D000818:Animals; D001230:Aspergillus / Q000737:chemistry* / Q000187:drug effects; D001374:Azacitidine / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005285:Fermentation; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D000081223:Polycyclic Sesquiterpenes; D000067996:RAW 264.7 Cells; D064210:Secondary Metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C018286:eremophilane compounds; D009569:Nitric Oxide; D001374:Azacitidine
ECD; epigenetic modification; eremophilane; marine fungus; nitric oxide inhibitory activity