AUTHOR=Wu Jing-Shuai , Shi Xiao-Hui , Zhang Ya-Hui , Yu Jia-Yin , Fu Xiu-Mei , Li Xin , Chen Kai-Xian , Guo Yue-Wei , Shao Chang-Lun , Wang Chang-Yun 

TITLE=Co-cultivation With 5-Azacytidine Induced New Metabolites From the Zoanthid-Derived Fungus Cochliobolus lunatus

JOURNAL=Frontiers in Chemistry

VOLUME=7

YEAR=2019

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2019.00763

DOI=10.3389/fchem.2019.00763

ISSN=2296-2646

ABSTRACT=<p>The zoanthid-derived fungus <italic>Cochliobolus lunatus</italic> (TA26-46) has been proven to be a source of bioactive 14-membered resorcylic acid lactones (RALs). In the present study, chemical epigenetic manipulation was applied to this fungal strain with a DNA methyltransferase inhibitor resulting in the significant changes of the secondary metabolites. Cultivation of <italic>C. lunatus</italic> (TA26-46) with 10 μM 5-azacytidine in Czapek-Dox liquid medium led to the isolation of new types of metabolites, including two α-pyrones, cochliobopyrones A (<bold>1</bold>) and B (<bold>2</bold>), along with three isocoumarins (<bold>3</bold>–<bold>5</bold>) and one chromone (<bold>6</bold>). The planar structures of the new compounds (<bold>1</bold>–<bold>2</bold>) were elucidated by comprehensive analyses of NMR and HRESIMS data. Their challenging relative configurations were established by a combination of acetonide reaction, coupling constants and NOESY correlations analysis, and DP4+ probability calculation. Their absolute configurations were determined by comparing with the ECD calculation data of the fragment molecules, 6-(1,2-dihydroxypropyl)-4-methoxy-2<italic>H</italic>-pyran-2-ones. It is the first time to obtain α<italic>-pyrone</italic> compounds with the epoxy ring or bromine atom on the seven-numbered side chain. It could be concluded that chemical epigenetic agents could induce <italic>C. lunatus</italic> to produce new types of secondary metabolites differing from its original products (RALs).</p>