Epigenetic modifier induced enhancement of fumiquinazoline C production in Aspergillus fumigatus (GA-L7): an endophytic fungus from Grewia asiatica L.

Ankita Magotra,Manoj Kushwaha,Ajai Prakash Gupta,Chand Raina,Asha Chaubey,Praveen Awasthi,Bhahwal A Shah,Sumit G Gandhi,Manjeet Kumar

doi:10.1186/s13568-017-0343-z

Abstract

Present study relates to the effect of valproic acid, an epigenetic modifier on the metabolic profile of Aspergillus fumigatus (GA-L7), an endophytic fungus isolated from Grewia asiatica L. Seven secondary metabolites were isolated from A. fumigatus (GA-L7) which were identified as: pseurotin A, pseurotin D, pseurotin F2, fumagillin, tryprostatin C, gliotoxin and bis(methylthio)gliotoxin. Addition of valproic acid in the growth medium resulted in the alteration of secondary metabolic profile with an enhanced production of a metabolite, fumiquinazoline C by tenfolds. In order to assess the effect of valproic acid on the biosynthetic pathway of fumiquinazoline C, we studied the expression of the genes involved in its biosynthesis, both in the valproic acid treated and untreated control culture. The results revealed that all the genes i.e. Afua_6g 12040, Afua_6g 12050, Afua_6g 12060, Afua_6g 12070 and Afua_6g 12080, involved in the biosynthesis of fumiquinazoline C were overexpressed significantly by 7.5, 8.8, 3.4, 5.6 and 2.1 folds respectively, resulting in overall enhancement of fumiquinazoline C production by about tenfolds.

Highlights

Fungal endophytes produce a myriad bioactive class of compounds like alkaloids, terpenoids, steroids, benzopyranones, chinones, flavonoids, phenolic acids, quinones, tetralones, xanthones, and long chain peptides with a wide range of activities including anti-microbial, anticancer, immunosuppressant etc. (Nalli et al 2015; Zhao et al 2011)
Epigenetic modifications using chemical inhibitors (HDAC or DNA methyltransferase (DNMT) inhibitors) or inducers are found to be effective in stimulating the Magotra et al AMB Expr (2017) 7:43 transcription of attenuated or silenced biosynthetic gene clusters, thereby resulting in the production or enhancement of a variety of secondary metabolites (Cichewicz 2010) e.g. Cladosporium cladosporioides when treated with histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA), led to the isolation of new cladochromes F, cladochromes G and calphostin B which was the first report of its co-occurrence with perylenequinones from a single source (Williams et al 2008)
We have studied the effect of an epigenetic modifier, valproic acid on A. fumigatus (GA-L7), an endophyte isolated from Grewia asiatica L., from which seven compounds were isolated under normal growth conditions

Summary

Introduction

Fungal endophytes produce a myriad bioactive class of compounds like alkaloids, terpenoids, steroids, benzopyranones, chinones, flavonoids, phenolic acids, quinones, tetralones, xanthones, and long chain peptides with a wide range of activities including anti-microbial, anticancer, immunosuppressant etc. (Nalli et al 2015; Zhao et al 2011). Epigenetic modifications using chemical inhibitors (HDAC or DNMT inhibitors) or inducers are found to be effective in stimulating the Magotra et al AMB Expr (2017) 7:43 transcription of attenuated or silenced biosynthetic gene clusters, thereby resulting in the production or enhancement of a variety of secondary metabolites (Cichewicz 2010) e.g. Cladosporium cladosporioides when treated with HDAC inhibitor suberoylanilide hydroxamic acid (SAHA), led to the isolation of new cladochromes F, cladochromes G and calphostin B which was the first report of its co-occurrence with perylenequinones from a single source (Williams et al 2008). Bioactive molecules like 12β-hydroxy-13α-methoxyverruculogen TR-2, fumitremorgin B, verruculogen, and helvolic acid have been isolated which showed potent antifungal activity (Li et al 2012)

Methods

Results

Conclusion