Structure-guided identification and designing of novel, potential anti-fungal agents against ArOYE6 to control the fungal diseases in crops
Implementing Organization
Jawaharlal Nehru University
Principal Investigator
Prof. Praveen Kumar Verma
Jawaharlal Nehru University
CO-Principal Investigator
Dr. Neel Sarovar Bhavesh
International Centre For Genetic Engineering And Biotechnology, Delhi-110067
About
Fungi pose a significant threat to food crops and human lives worldwide. The search for novel fungicides is the primary area of research, and the incidence of fungicide resistance is worsening. To tackle this issue, researchers are exploring new potential anti-fungal candidates by screening molecules for anti-fungal activity or designing specific inhibitors against known target proteins of pathogens. Class III Old Yellow Enzymes (OYEs) found in pathogenic filamentous fungi offer a potential target for developing novel anti-fungal agents. A recent study determined the high resolution crystal structure of ArOYE6, a class III member from a phytopathogenic fungus Ascochyta rabiei. Studies on A. rabiei identified ArOYE6 as a potential player involved in fungal oxidative stress response, which is up-regulated upon oxidative stress exposure and during chickpea infection. These determinants of oxidative stress response are critical for fungal virulence and present good targets for drug design. The project aims to harness the structural intricacies of ArOYE6 for designing class III-specific inhibitors to control crop fungal diseases. The Chickpea-Ascochyta and Wheat-Bipolaris host-pathosystems will be used to develop proof of concept. The exclusive presence of class III OYEs in phytopathogenic fungi would enable conferring target-specificity, and the conservation of class III OYEs among phytopathogenic fungi could offer novel ways to control a broad spectrum of devastating fungal diseases in economically important crops. This study would deliver potential candidates that can serve as integral components in the combinatorial approach to minimize the chances of fungicide resistance development.