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

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

doi:10.3389/fchem.2019.00763

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).

Highlights

Marine fungi have been proved to be able to produce a wealth of structurally novel and biologically potent secondary metabolites (Jin et al, 2016; Blunt et al, 2018)
To explore the biosynthetic potential of this fungus, chemical epigenetic manipulation was conducted by using DNA methyltransferase inhibitors and histone deacetylase inhibitors to treat this fungus cultured on starch solid medium, resulting in the production of new metabolites, including diethylene glycol phthalate esters (Chen et al, 2016) and brominated resorcylic acid lactones (RALs) (Zhang et al, 2014)
It was founded that 5- azacytidine and SAHA could result in the significant changes of the secondary metabolites

Summary

INTRODUCTION

Marine fungi have been proved to be able to produce a wealth of structurally novel and biologically potent secondary metabolites (Jin et al, 2016; Blunt et al, 2018). 5-azacytidine Induced New Fungal Metabolites chemical epigenetic manipulation has been widely used as an effective and handy approach to harvest cryptic secondary metabolites from microbes (Cichewicz, 2010; Cherblanc et al, 2013) This approach has proven to be able to induce new metabolic pathway to produce new type of compounds. To explore the biosynthetic potential of this fungus, chemical epigenetic manipulation was conducted by using DNA methyltransferase inhibitors and histone deacetylase inhibitors to treat this fungus cultured on starch solid medium, resulting in the production of new metabolites, including diethylene glycol phthalate esters (Chen et al, 2016) and brominated RALs (Zhang et al, 2014). We reported the chemical epigenetic manipulation of the strain, and the isolation, structure elucidation, and bioactivity evaluation of the induced metabolites

MATERIALS AND METHODS

RESULTS

DATA AVAILABILITY STATEMENT

CONCLUSION