Epigenetic modulation of secondary metabolite profiles in Aspergillus calidoustus and Aspergillus westerdijkiae through histone deacetylase (HDAC) inhibition by vorinostat

2020 ◽  
Vol 73 (6) ◽  
pp. 410-413 ◽  
Author(s):  
Mohammed Aldholmi ◽  
Barrie Wilkinson ◽  
A. Ganesan
Keyword(s):  
Histone Deacetylase ◽  
Secondary Metabolite ◽  
Hdac Inhibition ◽  
Metabolite Profiles ◽  
Aspergillus Westerdijkiae ◽  
Epigenetic Modulation

scholarly journals Chitin Degradation Machinery and Secondary Metabolite Profiles in the Marine Bacterium Pseudoalteromonas rubra S4059

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 108
Author(s):  
Xiyan Wang ◽  
Thomas Isbrandt ◽  
Mikael Lenz Strube ◽  
Sara Skøtt Paulsen ◽  
Maike Wennekers Nielsen ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Genetic Manipulation ◽  
Genome Mining ◽  
Hydrolytic Enzymes ◽  
Metabolite Profile ◽  
Chitinolytic Enzyme ◽  
Chitin Degradation ◽  
Metabolite Profiles ◽  
Bioactive Potential ◽  
Pseudoalteromonas Rubra

Genome mining of pigmented Pseudoalteromonas has revealed a large potential for the production of bioactive compounds and hydrolytic enzymes. The purpose of the present study was to explore this bioactivity potential in a potent antibiotic and enzyme producer, Pseudoalteromonas rubra strain S4059. Proteomic analyses (data are available via ProteomeXchange with identifier PXD023249) indicated that a highly efficient chitin degradation machinery was present in the red-pigmented P. rubra S4059 when grown on chitin. Four GH18 chitinases and two GH20 hexosaminidases were significantly upregulated under these conditions. GH19 chitinases, which are not common in bacteria, are consistently found in pigmented Pseudoalteromonas, and in S4059, GH19 was only detected when the bacterium was grown on chitin. To explore the possible role of GH19 in pigmented Pseudoalteromonas, we developed a protocol for genetic manipulation of S4059 and deleted the GH19 chitinase, and compared phenotypes of the mutant and wild type. However, none of the chitin degrading ability, secondary metabolite profile, or biofilm-forming capacity was affected by GH19 deletion. In conclusion, we developed a genetic manipulation protocol that can be used to unravel the bioactive potential of pigmented pseudoalteromonads. An efficient chitinolytic enzyme cocktail was identified in S4059, suggesting that this strain could be a candidate with industrial potential.

scholarly journals Genome-Wide STAT3 Binding Analysis after Histone Deacetylase Inhibition Reveals Novel Target Genes in Dendritic Cells

2016 ◽  
Vol 9 (2) ◽  
pp. 126-144 ◽  
Author(s):  
Yaping Sun ◽  
Matthew Iyer ◽  
Richard McEachin ◽  
Meng Zhao ◽  
Yi-Mi Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dendritic Cells ◽  
Histone Deacetylase ◽  
Antigen Processing ◽  
Target Genes ◽  
Hdac Inhibition ◽  
Histone Deacetylase Inhibition ◽  
Immune Effector ◽  
Chip Sequencing ◽  
Genome Wide

STAT3 is a master transcriptional regulator that plays an important role in the induction of both immune activation and immune tolerance in dendritic cells (DCs). The transcriptional targets of STAT3 in promoting DC activation are becoming increasingly understood; however, the mechanisms underpinning its role in causing DC suppression remain largely unknown. To determine the functional gene targets of STAT3, we compared the genome-wide binding of STAT3 using ChIP sequencing coupled with gene expression microarrays to determine STAT3-dependent gene regulation in DCs after histone deacetylase (HDAC) inhibition. HDAC inhibition boosted the ability of STAT3 to bind to distinct DNA targets and regulate gene expression. Among the top 500 STAT3 binding sites, the frequency of canonical motifs was significantly higher than that of noncanonical motifs. Functional analysis revealed that after treatment with an HDAC inhibitor, the upregulated STAT3 target genes were those that were primarily the negative regulators of proinflammatory cytokines and those in the IL-10 signaling pathway. The downregulated STAT3-dependent targets were those involved in immune effector processes and antigen processing/presentation. The expression and functional relevance of these genes were validated. Specifically, functional studies confirmed that the upregulation of IL-10Ra by STAT3 contributed to the suppressive function of DCs following HDAC inhibition.

scholarly journals Enhancing the anti-tumor activity of ErbB blockade with histone deacetylase (HDAC) inhibition

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 3029-3029
Author(s):  
P. Chinnaiyan ◽  
S. Varambally ◽  
S. A. Tomlins ◽  
S. Huang ◽  
A. M. Chinnaiyan ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Hdac Inhibition ◽  
Anti Tumor Activity

scholarly journals Different Secondary Metabolite Profiles of Phylogenetically almost Identical Streptomyces griseus Strains Originating from Geographically Remote Locations

2019 ◽  
Vol 7 (6) ◽  
pp. 166 ◽  
Author(s):  
Ignacio Sottorff ◽  
Jutta Wiese ◽  
Matthias Lipfert ◽  
Nils Preußke ◽  
Frank D. Sönnichsen ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
16S Rrna ◽  
16S Rrna Gene ◽  
Secondary Metabolite ◽  
Streptomyces Griseus ◽  
Garden Soil ◽  
Rrna Gene ◽  
Gene Sequences ◽  
16S Rrna Gene Sequences ◽  
Metabolite Profiles

As Streptomyces have shown an outstanding capacity for drug production, different campaigns in geographically distant locations currently aim to isolate new antibiotic producers. However, many of these newly isolated Streptomyces strains are classified as identical to already described species. Nevertheless, as discrepancies in terms of secondary metabolites and morphology are possible, we compared two Streptomyces strains with identical 16S rRNA gene sequences but geographically distant origins. Chosen were an Easter Island Streptomyces isolate (Streptomyces sp. SN25_8.1) and the next related type strain, which is Streptomyces griseus subsp. griseus DSM 40236T isolated from Russian garden soil. Compared traits included phylogenetic relatedness based on 16S rRNA gene sequences, macro and microscopic morphology, antibiotic activity and secondary metabolite profiles. Both Streptomyces strains shared several common features, such as morphology and core secondary metabolite production. They revealed differences in pigmentation and in the production of accessory secondary metabolites which appear to be strain-specific. In conclusion, despite identical 16S rRNA classification Streptomyces strains can present different secondary metabolite profiles and may well be valuable for consideration in processes for drug discovery.

scholarly journals HDAC8 Inhibition Reduces Lesional Iba-1+ Cell Infiltration after Spinal Cord Injury without Effects on Functional Recovery

2020 ◽  
Vol 21 (12) ◽  
pp. 4539
Author(s):  
Sven Hendrix ◽  
Selien Sanchez ◽  
Elissia Ventriglia ◽  
Stefanie Lemmens
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Valproic Acid ◽  
Side Effects ◽  
Histone Deacetylase ◽  
Functional Recovery ◽  
Hdac Inhibition ◽  
Beneficial Effects ◽  
Cord Injury ◽  
Classically Activated

Pan-histone deacetylase (HDAC) inhibition with valproic acid (VPA) has beneficial effects after spinal cord injury (SCI), although with side effects. We focused on specific HDAC8 inhibition, because it is known to reduce anti-inflammatory mediators produced by macrophages (Mφ). We hypothesized that HDAC8 inhibition improves functional recovery after SCI by reducing pro-inflammatory classically activated Mφ. Specific HDAC8 inhibition with PCI-34051 reduced the numbers of perilesional Mφ as measured by histological analyses, but did not improve functional recovery (Basso Mouse Scale). We could not reproduce the published improvement of functional recovery described in contusion SCI models using VPA in our T-cut hemisection SCI model. The presence of spared fibers might be the underlying reason for the conflicting data in different SCI models.

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