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

Abstract

The zoanthid-derived fungus Cochliobolus lunatus (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 C. lunatus (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 (1) and B (2), along with three isocoumarins (3–5) and one chromone (6). The planar structures of the new compounds (1–2) 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-2H-pyran-2-ones. It is the first time to obtain α-pyrone compounds with the epoxy ring or bromine atom on the seven-numbered side chain. It could be concluded that chemical epigenetic agents could induce C. lunatus to produce new types of secondary metabolites differing from its original products (RALs).

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).…”

Study on Secondary Metabolites of Endophytic Fungus, Aspergillus fumigatus, from Crocus sativus L. Guided byUHPLC-HRMS/MS-Based Molecular Network

“…On the basis of GNPS-MN results, 15 known compounds were isolated, and their structures are described in Figure 4 . Through comparison of the NMR spectroscopic data with that reported in the literature, the known compounds were identified as emodin (1) [ 34 ], verruculogen (2) [ 35 ], monomethylsulochrin (3) [ 36 ], questin (4) [ 34 ], fumitremorgins B–C (5, 7) [ 37 ], cyclotryprostatins A-B (10, 6) [ 38 ], 10-methyl-9Z-octadecenoic glyceride (12) [ 39 ], pyripyropene E (13) [ 40 ], helvolic acid (14) [ 41 ], 12,13-dihydroxyfumitremorgin C (8) [ 35 ], 6-hydroxy-8-methoxy-3-methylisocoumarin (11) [ 42 ], 13-dehydroxycyclotryprostatin C (9) [ 43 ], and spirotryprostatin A (15) [ 44 ]. Notably, compounds 11 and 12 have not been isolated from the genus Aspergillus .…”

Overexpression of Global Regulator Talae1 Leads to the Discovery of New Antifungal Polyketides From Endophytic Fungus Trichoderma afroharzianum

“…A plausible biosynthetic pathway for 1 and 2 is proposed as shown in Figure 6 . The polyketide chain primed with one acetyl-CoA starter unit and six malonyl-CoA extender units was selectively enolized, hydroxylated, methylated, cyclized, and finally released as the intermediate a ( Wu et al, 2019 ). Compounds 1 and 2 are proposed to be generated by further decarboxylation and O-methylation ( Shaw et al, 2015 ; Lebe and Cox, 2019 ).…”