The DNA‐methyltransferase inhibitor 5‐aza‐2‐deoxycytidine affects Humicola grisea enzyme activities and the glucose‐mediated gene repression

Abstract

Humicola grisea var. thermoidea (Hgvt) is a thermophilic ascomycete that produces lignocellulolytic enzymes and it is proposed for the conversion of agricultural residues into useful byproducts. Drugs that inhibit the DNA methyltransferases (DNMTs) activity are employed in epigenetic studies but nothing is known about a possible effect on the production of fungal enzymes. We evaluated the effect of 5-aza-2'-deoxycytidine (5-Aza; a chemical inhibitor of DNMTs activity) on the secreted enzyme activity and on the transcription of cellulase and xylanase genes from Hgvt grown in agricultural residues and in glucose. Upon cultivation on wheat bran (WB), the drug provoked an increase in the xylanase activity at 96 h. When Hgvt was grown in glucose (GLU), a repressor of Hgvt glycosyl hydrolase genes, 5-Aza led to increased transcript accumulation for the cellobiohydrolases and for the xyn2 xylanase genes. In WB, 5-Aza enhanced the expression of the transcription factor CreA gene. Growth on WB or GLU, in presence of 5-Aza, led to a significant increase in transcripts of the pH-response regulator PacC gene. To our knowledge, this is the first report on the effect of a DNMT inhibitor in the production of fungal plant cell wall degradation enzymes.

Developments and opportunities in fungal strain engineering for the production of novel enzymes and enzyme cocktails for plant biomass degradation

“…Indications for a role of DNA methylation in the expression of genes encoding plant biomass degrading enzymes have also been reported using an inhibitor of DNA methyltransferase, 5-aza-2'deoxycitidine (Manfrão-Netto et al, 2018). In the presence of this inhibitor xylanase activity was increased during growth on wheat bran, while expression of cellobiohydrolase and xylanase encoding genes was increased during growth on glucose.…”

DNA Methyltransferases: From Evolution to Clinical Applications

“…Fungi is a biological kingdom that has let us see the importance of metabolite production and the diversity of various types of metabolisms that have evolved to survive on every external condition. Although in fungi [ 80 ], homolog DNMTs have been poorly experimentally studied, DIM-2, DNMT1, DNMT5, and RID are present [ 43 , 80 ] and have a function in metabolism and secondary metabolite production: of xylanase, a plant enzyme function in cell wall degradation of Humicola grisea [ 41 ]; the production of cytochalasin E, an antibacterial and anti-angiogenic compound in Aspergillus clavatus [ 42 ], and the production of aflatoxin in Aspergillus flavus [ 81 ]. Fungi are a big group of living beings.…”

Drugs Targeting Epigenetic Modifications and Plausible Therapeutic Strategies Against Colorectal Cancer

“…Decitabine treatment suppressed the invasion ability of CRC lymph node metastasis-derived SW620 cells as well as oxaliplatin-resistant SW620 cells. Cells regained the epithelial characteristic that was indicated by upregulation of E-cadherin, miR-200C, and miR-141 (Tanaka et al, 2015; Manfrão-Netto et al, 2018). It has also been used in combination with other drugs like gefitinib and azacitidine as the effective treatment approach for CRC (Müller and Florek, 2010; Gerecke et al, 2018).…”