Induction of secondary metabolite production in endophytic fungi isolated from Albizia adianthifolia using multiple small compounds involved in fungal chromatin remodeling.

Abstract

Fungi are an inexhaustible source of unexplored bioactive secondary metabolites that have been useful to humans as pharmaceuticals and other valuable products. The unexplored arsenal of secondary metabolites from fungi and the growing problem of antibiotic resistance have led to the search for novel bioactive secondary metabolites in fungi from unique niches. Endophytic fungi are an unexplored niche of fungi that have a special mutualistic relationship with their hosts. Endophytic fungi and medicinal plants' relationship has received attention as endophytic fungi have been shown to produce bioactive secondary metabolites with a profile similar to secondary metabolites from their host medicinal plants. Despite the potential of endophytic fungi as an arsenal for novel pharmacological important secondary metabolites, they remain hugely unexplored due to the cryptic or silenced nature of some biosynthetic gene clusters coding for secondary metabolites. The genes that code for secondary metabolites are arranged in clusters known as biosynthetic gene clusters. Some of these biosynthetic gene clusters are sequestered away from transcription factors; thus, they are not transcribed under standard laboratory conditions. Small-molecule modifiers have been recognized as an important way of activating these silenced genes through epigenetic regulation of the chromatin. Thus, the present study sought to induce secondary metabolite production in nine endophytic fungi isolated from Albizia adianthifolia using multiple small compounds (valproic acid, quercetin, sodium butyrate, and trimethoprim) involved in fungal chromatin remodeling. The secondary metabolites were assayed for their antibacterial activity against Staphylococcus aureus, Escherichia coli, Mycobacterium smegmatis, Enterococcus faecalis, and Klebsiella pneumoniae. Antibacterial activity was observed from two untreated and quercetin and trimethoprim-treated endophytic fungi identified through nucleotide sequencing of the internal transcribed spacer of ribosomal DNA as Alternaria sp against S. aureus, E. faecalis, and M. smegmatis. Significant antibacterial activity was observed for quercetin and trimethoprim23 treated Alternaria alternata and Alternata brassicicola. However, the valproic acid-treated A. alternata showed slight antibacterial activity against the S. aureus, E. faecalis, and M. smegmatis, while no antibacterial activity was observed for valproic acid-treated A. brassicicola. No antibacterial activity was observed with sodium butyrate-treated A. alternata and A. brassicicola. The findings of this study add to the pool of studies aimed at discovering new drugs from endophytic fungi to address antimicrobial resistance. Future studies on high performance liquid chromatography to identify the active secondary metabolites from A. brassicicola and A. alternata will be done. Also, future studies to fully assess the mechanisms of chromatin remodeling in the active endophytic fungi will assist in identifying small molecule modifiers that can activate secondary metabolite production in endophytic fungi.