Epigenetic modifications for developing a commercial isolate from endophytic Fusarium sp. for Epigallocatechin gallate (EGCG) production

Abstract

Parkinson’s Disease (PD) is a progressive neurodegenerative condition, characterized by motor dysfunctions. The clustering of certain genes, alpha-synuclein’s misfolding and aggregation creates fibril and oligomeric formations, are reported to be the key contributor to the development of PD. The existing therapies for PD mainly focus on managing symptoms and dopamine replacement rather than halting or reversing the progression of PD. Research indicates the therapeutic potential of certain plant derived polyphenolic compounds, specifically Epigallocatechin gallate (EGCG), that have the ability to prevent α-synuclein aggregation, effectively halting the onset of disease at its earliest stages. These polyphenolic compounds are capable of inhibiting α-synuclein aggregation and reducing oxidative stress, positioning them as promising candidates for neuroprotective drug development, however its limited natural occurrence restricts its utilization in therapeutic approaches. This study focuses on improving the production of EGCG in endophytic fungi, through the application of epigenetic modifications using 5-Azacytidine and Butyric acid. The crude extracts were subjected to various concentrations of modulators. The findings indicated maximum yield of tannic acid at 10M AZA and 200M butyric acid. EGCG showed an increase in yield at the same concentrations, as determined using spectrophotometric analysis. Treated extracts also exhibited enhanced antioxidant potential and increased total phenolic content, depicting enhanced antioxidant potential The results confirm the potential of epigenetic modulators as non-recombinant method for enhancing secondary metabolites production, making scalable and sustainable production of EGCG possible for therapeutic applications, specifically in neurodegenerative disorders such as PD. Keywords: Parkinson’s Disease, -Synuclein, Epigallocatechin gallate, Polyphenolic compounds, Endophytic Fungi, Epigenetic modifications