Molecular Docking and Comparative Inhibitory Efficacy of Naturally Occurring Compounds on Vegetative Growth and Deoxynivalenol Biosynthesis in Fusarium culmorum

Abstract

The fungal pathogen Fusarium culmorum causes Fusarium head blight in cereals, resulting in yield loss and contamination of the grain by type B trichothecene mycotoxins such as deoxynivalenol (DON), and its acetylated derivatives. Synthesis of trichothecenes is driven by a trichodiene synthase (TRI5) that converts farnesyl pyrophosphate (FPP) to trichodiene. In this work, 15 naturally occurring compounds that belong to the structural phenol and hydroxylated biphenyl classes were tested in vitro and in planta (durum wheat) to determine their inhibitory activity towards TRI5. In vitro analysis highlighted the fungicidal effect of these compounds when applied at 0.25 mM. Greenhouse assays showed a strong inhibitory activity of octyl gallate 5, honokiol 13 and the combination propyl gallate 4 + thymol 7 on trichothecene biosynthesis. Docking analyses were run on the 3D model of F. culmorum TRI5 containing the inorganic pyrophosphate (PPi) or FPP. Significant ligand affinities with TRI-PPi and TRI-FPP were observed for the same sites for almost all compounds, with 1 and 2 as privileged sites. Octyl gallate 5 and honokiol 13 interacted almost exclusively with sites 1 and 2, by concurrently activating strong H-bonds with common sets of amino acids. These results open new perspectives for the targeted search of naturally occurring compounds that may find practical application in the eco-friendly control of FHB in wheat.

Bioprospecting Phenols as Inhibitors of Trichothecene-Producing Fusarium: Sustainable Approaches to the Management of Wheat Pathogens

“…For instance, Siranidou et al [223] reported a synergistic antifungal effect of p-coumaric with ferulic acid in reducing the mycelial growth of F. culmorum. An equimolar combination of propyl gallate and thymol tested at a final concentration of 0.25 mM proved a strong inhibitor of trichothecenes both in vitro and in plants [224]. Oufensou et al [166] tested an equimolar solution of thymol and magnolol, which had an additive effect on F. graminearum, possibly due to the different mode of action of the two compounds, or/and to the ability of one compound of the mixture to cross the fungal membrane, thereby improving the delivery of the other compound.…”

“…Another computational study on TRI5 protein has been recently carried out by Oufensou et al [224]. A set of 15 naturally occurring compounds belonging to cinnamic acids, gallic esters, terpenes, phenylpropanoids, and 1 phenylethanone was selected for docking onto TRI5.…”

Mycotoxins’ Toxicological Mechanisms Involving Humans, Livestock and Their Associated Health Concerns: A Review

“…In wheat, Fusarium head blight caused by F. culmorum or F. graminearum infection starts from the grain head exterior and passes into the interior. Accordingly, DON is mostly identified in the chaff and the kernel outer layers [ 115 , 116 ]. Grain dusts could have high DON concentrations and other mycotoxins in unsafe levels, which may not be the same in kernels.…”

“…DON has direct toxicity through its epoxide moiety and consequently requires no metabolic activation for exerting its biological effect. Low-level exposure to trichothecene in animals modulates the expression of several chemokines and cytokines, which are key immune function regulators [ 116 , 117 ]. DON exposure results in upregulating mRNAs responsible for producing chemokines, cytokines, and other proteins associated with the immune system, which can also cause gene transcription.…”

“…Activating processes resulting in a ribotoxic stress response are also connected to the DON activation of MAPK, and they are initiated by other inhibitors of translation, which, like deoxynivalenol, damage or bind to a specific region at the 28S rRNA 3′ end. Ribosomes play important roles in the ribotoxic stress response through functioning as a scaffold for the interaction between several MAPKs [ 18 , 116 ].…”