Epigenetic modifier-induced biosynthesis of novel fusaric acid derivatives in endophytic fungi from Datura stramonium L.

Abstract

Abstract:The treatment of fungi with DNA methyltransferase (DNMT) and/or histone deacetylase (HDAC) inhibitors is a promising way to activate secondary metabolite biosynthetic pathways that are dormant under normal conditions. In this study, we included an HDAC inhibitor, suberoylanilide hydroxamic acid (SBHA), in the culture medium of endophytic fungi isolated from the medicinal plant Datura stramonium L. The production of two compounds was induced in the culture supplemented with SBHA, and their structures were determined to be the fusaric acid derivatives 5-butyl-6-oxo-1,6-dihydropyridine-2-carboxylic acid and 5-(but-9-enyl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid. The result confirmed that the use of chemical epigenetic modifiers is an effective technique for promoting the expression of silent biosynthetic pathways to produce unique secondary metabolites.

Multicomponent Analysis of the Differential Induction of Secondary Metabolite Profiles in Fungal Endophytes

“…The majority of these epigenetic studies report the effect of using hydroxamic-acid compounds, such as SAHA (8), with similar HDAC inhibitory effects; e.g.,: the production of a new fungal biosynthetic cyclodepsipeptide (EMG-556) by Microascus sp. when cultured with SAHA [9], the production of new anti-infective cytosporones by the marine fungus Leucostoma persoonii [10] or, the biosynthesis of novel fusaric acid derivatives by the Datura stramonium endophyte when SBHA was added to its production medium [11].…”

Endophytic Fungi as a Source of Novel Metabolites

“…Those approaches have been also applied to the endophytes cultures [99][100][101][102][103][104][105][106] and the following examples confirm that the secondary metabolism remodeling by cultivation-dependent approaches may yield new metabolites [103][104][105].…”

Endophytes as in vitro production platforms of high value plant secondary metabolites

“…• 5-Butyl-6-oxo-1,6-dihydropyridine-2-carboxylic acid • 5-(But-9-enyl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid Chen et al (2013) Sodium butyrate (HDAC inhibitor) Leucostoma persoonii • Novel compound -cytosporone R • Enhanced production of known cytosporones B (360%), C (580%) and E (890%) Beau et al (2012) 5-Azacytidine (DNMT inhibitor) and/or suberoylanilide hydroxamic acid (HDAC inhibitor)…”