Antifungal activity and molecular mechanisms of mulberrin derivatives against Colletotrichum gloeosporioides for mango storage

In this work, by using high throughput virtual screening and bioactivity assays, this work revealed that three natural compounds, mulberrin (Mul) exhibiting the highest anti-CYP51 activity, isoxanthohumol and (s)-isopsoralen markedly inhibited 14α-demethylase (a pivotal biosynthetic enzyme involved in the biosynthesis of ergosterol) in Colletotrichum gloeosporioides . Results of computational biology analysis demonstrated that, among the three inhibitors bound to the catalytic pocket of CYP51, Mul showed a closer distance with heme in CYP51 and a stronger binding free energy with CYP51. In vitro tests, Mul demonstrated excellent anti- Colletotrichum gloeosporioides activity by inhibiting CYP51 activity. Notably, Mul treatment decreased the bioactivity of CYP51, thereby increasing cell membrane permeability and cell death. Moreover, Mul treatment significantly prolonged the preservation period of fruits. These results suggest that Mul suppresses anthracnose in postharvest mango by inhibiting the growth of Colletotrichum gloeosporioides and can be used as a potential natural preserving agent. • Mul exhibited the excellent anti-CYP51 of C. gloeosporioides activity. • Mul binds to the catalytic active pocket of CYP51 as the competition inhibitory. • Mul apparently inhibit the growth of C. gloeosporioides by the binding with CYP51. • The shelf life of fruit infection model could be significantly prolonged by Mul.