Acetyl-CoA carboxylase as potential molecular target of dimethyl trisulfide on inhibiting the Aspergillus flavus growth and aflatoxins production

Abstract

Aspergillus flavus and the produced aflatoxins are common hazardous contaminants in grains and food, which generated great damage to food security and human health. Acetyl-CoA carboxylase (ACC), catalyzing acetyl-CoA to malonyl-CoA, is the first and speed-determining step in fatty acid biosynthesis (cell membrane composition) and aflatoxins biosynthesis process in A. flavus. Here, we demonstrated that dimethyl trisulfide (DMTS), emitted from bacteria, could interact with ACC, decrease the enzymatic activity from 377.62 to 191.42 kat/g in vitro, down-regulate the expression of ACC and other important genes in fatty acid and aflatoxin biosynthesis pathway, reduce the content of hexadecanoic acid, octadecanoic acid and eicosanoic acid, and finally prevent A. flavus growth and aflatoxins production. Two binding sites containing 19 amino acids were detected between DMTS and ACC through molecular docking analysis. These amino acids were highly conserved in different filamentous fungi, which accounted for the broad antifungal spectrum of DMTS. Therefore, we concluded that ACC is the molecular target of DMTS on A. flavus growth and aflatoxins production. These results elucidate the inhibitory mechanism of DMTS on fungal pathogens, and provide basic theories for the development of novel antifungal agents.