Analysis of the synergistic antifungal mechanism of small molecular combinations of essential oils at the molecular level

The bacteriostatic concentration of essential oil (EO) in practical application is usually higher than the flavor threshold, resulting in a lack of balance between bacteriostatic concentration and flavor, which has become the bottleneck of its application in the field of agriculture products. One of the effective ways to solve this problem is the synergistic antibacterial effect of the active components of EO. In this paper, molecular docking, independent gradient model (IGM) and symmetric matching perturbation theory (SAPT) are combined for the first time to investigated the molecular mechanism of eugenol and citral small molecules (EAC) against Aspergillus niger. The results show that EAC can combine with β-(1,3)-glucan synthase and chitin synthase proteins, and then destroy the integrity of cell wall, in which the trans-citral has the best affinity with these two enzyme proteins. In addition, EAC can bind to tryptophan, tyrosine and phenylalanine in cell membrane. The binding of citral small molecules to these three amino acids is mainly hydrogen bond, while the binding force of eugenol to them is mainly van der Waals force or π-π interaction. Finally, the synergistic antifungal effect of EAC was confirmed by the damage of membrane proteins and the leakage of cell contents. In this combination, citral binds to the cell wall, which promotes the interaction between eugenol and cell membrane, and finally leads to the serious destruction of cell membrane. The above results show that EAC has the potential to be developed into a new type of agriculture products preservative with synergistic antifungal effect.