Activation of silent biosynthetic gene clusters and profiling of secondary metabolites secreted by Endophytic Fungi for use as potential anti-HIV agents.
Loading...
Date
2022
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
The continuous burden of Human Immunodeficiency Virus-1 in Sub-Saharan Africa, coupled
with the inability of antiretroviral agents to eradicate HIV-1 from viral reservoirs, the potential
risks of drug resistance development, and the development of adverse effects, emphasizes the
need to develop a new class of HIV-1 inhibitors. Here, we cultivated five endophytic fungi
isolated from Albizia adianthifolia with the addition of small epigenetic modifiers, sodium
butyrate and valproic acid, to induce the expression of biosynthetic gene clusters encoding
active secondary metabolites with probable anti-HIV activities. We identified a non-toxic crude
extract of the endophytic fungus Penicillium chrysogenum treated with sodium butyrate to
possess significantly greater anti-HIV activity than the untreated extracts. Single-round
fractionated extracts of treated P.chrysogenum showed potent anti-HIV activity with an IC₅₀ of
5.90 μg/mL and a 5-fold increase compared to the untreated fraction. The active fractionated
extracts were subjected to gas chromatography-mass spectrometry (GCMS), and more
bioactive compounds were detected in treated P.chrysogenum fractions than in untreated
fractions. These results indicate that treatment of endophytic fungi with small epigenetic
modifiers enhances the secretion of secondary metabolites with anti-HIV-1 properties,
acknowledging the feasibility of epigenetic modification as an innovative approach for the
discovery of cryptic fungal metabolites as therapeutic compounds
Description
Masters Degree. University of KwaZulu-Natal, Durban.