Epigenetic Induction of Secondary Metabolites Production in Endophytic Fungi Penicillium chrysogenum and GC-MS Analysis of Crude Metabolites with Anti-HIV-1 Activity

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 four endophytic fungal isolates from a medicinal plant, 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. Penicillium chrysogenum P03MB2 showed anti-HIV activity with an IC50 of 0.6024 µg/mL compared to untreated fungal crude extract (IC50 5.053 µg/mL) when treated with sodium butyrate. The profile of secondary metabolite compounds from the bioactive, partially purified extracts were identified by gas chromatography-mass spectrometry (GC-MS), and more bioactive compounds were detected in treated P. chrysogenum P03MB2 fractions than in untreated fractions. Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro (13.64%), cyclotrisiloxane, hexamethyl (8.18%), cyclotetrasiloxane, octamethyl (7.23%), cyclopentasiloxane, decamethyl (6.36%), quinoline, 1,2-dihydro-2,24-trimethyl (5.45%), propanenitrile (4.55%), deca-6,9-diene (4.55%), dibutyl phthalate (4.55%), and silane[1,1-dimethyl-2-propenyl)oxy]dimethyl (2.73%) were the most abundant compounds. These results indicate that treatment of endophytic fungi with small epigenetic modifiers enhances the secretion of secondary metabolites with stronger anti-HIV-1 properties, acknowledging the feasibility of epigenetic modification as an innovative approach for the discovery of cryptic fungal metabolites which can be developed into therapeutic compounds.

In vitro antioxidant and anticancer potential of intra-cellular ethyl acetate extract of marine-derived fungus Talaromyces tratensis SS10

“…Benzeneethanamine, N-[(pentafluorophenyl)methylene]beta.,3,4-tris[(trimethylsilyl) oxy]-is recorded in the T. tratensis ethyl acetate extract. This alkaloid is also recorded earlier in the crude extracts of Penicillium chrysogenum and has anti-HIV, antimicrobial, and antioxidant properties(Makhwitine et al, 2023).The compound cyclononasiloxane, octadecamethyl-is recorded in the T. tratensis ethyl acetate extract. Studies byLutfia et al (2021) also recorded the same compound in the ethyl acetate extracts of Zingiber griffithii rhizome and Hypomontagnella monticulosa Zg15SU mycelial extracts.…”

Anti-HIV Activity and Immunomodulatory Properties of Fractionated Crude Extracts of Alternaria alternata

“…The samples were then extracted with an equal volume of methanol (Sigma-Aldrich, Johannesburg, South Africa), followed by overnight shaking at 150 rpm using Rotory shaker (Reflecta Laboratory supplies, Glassware and Chemicals, Germiston, South Africa). All samples were then filtered with sterile gauze to remove mycelia and dried at 40 °C with a mild nitrogen gas steam [ 30 , 35 ]. Fungi-free cultures were included as controls and treated the same way as the experimental cultures to ensure that the observed activity resulted from fungal metabolites [ 36 ].…”

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

“…The biosynthesis of SMs in fungi can be stimulated either by external inducers (e.g., abiotic factors, plant-derived external elicitors, inducers from co-culture, and synthetic epige-netic modifiers) [288] or by internal inducers, which can act similarly to bacterial autoinducers [289,290]. Among these multiple influences for the production of SMs, various low molecular weight compounds (LMWCs) play an important role.…”