Cellular and non-target metabolomics approaches to understand the antifungal activity of methylaervine against Fusarium solani.

Abstract Botanical fungicides are promising replacements for pure chemical synthetic pesticides in agriculture and organic food production. Methylaervine with good physicochemical properties exhibited effective activity against F. solani (EC50 = 10.56 µM) better than the positive control thiophanate-methyl (EC50 = 27.94 µM). The activity changes of malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) showed that methylaervine could significantly induce lipid peroxidation and activate the antioxidant enzymes. According to the metabolomics analysis, fifty-one differential metabolites and two major antifungal-related pathways covering tricarboxylic acid (TCA) cycle and steroid biosynthesis were identified. Moreover, the disturbance for TCA cycle was validated by the activity changes of dehydrogenase (MDH) and succinate dehydrogenase (SDH) as well as docking simulation. Homology modeling and docking study revealed that hydrogen bonds and hydrophobic interactions played a vital role in methylaervine–protein stability. This study provided new insight into the antifungal activity of methylaervine, which is important for the development of novel botanical fungicides based on methylaervine.