Unraveling the potential role of bioactive molecules produced byTrichodermaspp. as inhibitors of tomatinase enzyme having an important role in wilting disease: anin-silicoapproach

Tomatinase; a saponin detoxification enzyme produced by Fusarium oxysporumf.sp. lycopersici is reported as a causative agent for wilting disease in tomato crops. The disease is instigated by inhibiting the activity of α-tomatine. Trichoderma spp. widely used as biocontrol agent play an essential role in plant growth and pathogen control. In the current study, an in-silico approach using substrate docking, molecular dynamics and MM/PBSA analysis was used to evaluate the potential role of bioactive metabolites produced by Trichoderma spp. The study aims to establish the efficacy of catalytic tendency of the bioactive metabolites to combat the effect of tomatinase enzyme employing α-tomatine as the substrate. By means of the integrated molecular modeling approach; novel bioactive metabolites namely, Trichodermamide B, Trichosetin and Virone were found to be the potential inhibitors against tomatinase enzyme secreted by Fusarium oxysporum f.sp. lycopersici. Molecular dynamic (MD) simulations displayed that the screened ligands bound tomatinase during 150 ns of MD simulations. Furthermore, the (MM-PBSA) free energy calculations depicted that screened molecules possess stable and favorable energies for Trichodermamide B (-7.1 kcal/mol), Trichosetin (-7.4 kcal/mol) and Virone (-7.9 kcal/mol) thereby instigating robust binding with the enzyme’s binding site. The results attained in this study, reflects that these bioactive metabolites may serve as potential substrates to control and inhibit the tomatinase enzyme; playing an integral role in combating the wilt disease.Communicated by Ramaswamy H. Sarma