Enrich Chemodiversity Of Fungal Metabolites By Epigenetic Modification Of Two Fungi Associated With Enteromorpha Prolifera

Epigenetics is the study of heritable changes in gene activity that are not causedby changes in the DNA sequence. Recently studies found in eukaryotes histoneacetylation, DNA demethylation and chromatin decompressed can promote geneactivation and improving gene transcription start. Therefor this idea was referenced tothe eukaryotic microrganisms fungi to activating and expression the silencing gene.In order to discovery new antibiotic activity compounds from the secondarymetabolites of the fermentation broth, according activate the marine fungus silencegene expression.31strains of fungi isolated from Enteromorpha prolifera in Qingdaowere evaluated with the combinatory method of chemical (TLC/HPLC) and bioactive(MCF-7) screening, which were regulated by DNA methylation inhibitors and histonedeacetylase inhibitors. Two of them were selected as the target strains for furtherstudy.The two strains were fermented with and without epigenetic modifiers,respectively. The whole broths were extracted with ethyl acetate to give fermentationproducts, which were subjected to extensive silica gel column chromatography,Sephadex LH-20and HPLC.49compounds were isolated from the two strains.The structures (Fig.0-1) were determined by means of spectral analysis (UV, IR,NMR, MS) methods. Among them,7known compounds were obtained fromAspergillus terreus OUCMDZ-2739cultured in general conditions and18differentcompounds were obtained from Aspergillus terreus OUCMDZ-2739cultured withTSA, including9new compounds (8–16). Eight compounds (26–33) obtained fromPenicillium sp. OUCMDZ-770cultured in general conditions, including two newcompounds (26–27). Eight different compounds (34–41) were obtained fromPenicillium sp. OUCMDZ-770cultured with VPA, including one new compound(34).All the compounds were evaluated for their antibacterial activity againstStaphylococcus aureus, Escherichia coli, Enterobacter aerogenes, Pseudomonasaeruginosa and Candida albicans; and cytotoxicity activity against A549, K562, andMCF-7cell lines. The result showed that compounds8,12,21showed weak antibiotic activities against Escherichia coli with MIC values of25μg/mL,50μg/mLand50μg/mL, respectively. Compounds30,32,41showed weak cytotoxicityactivities against A549cell line with IC50values of18,21and28μM, respectively.Compounds36,41showed weak antibiotic activities against Enterobacter aerogeneswith MIC values of50and30μg/mL, respectively.In this paper, we proved that use of histone deacetylase inhibitor TSA and VPAcan effectively activate the expression of marine fungus silence genes, which weresilence in laboratory culture conditions, showing its unique metabolic pathways,resulting in diversity structures, which were different from those cultured in normalculture conditions.