A methanolic extract of Zanthoxylum bungeanum modulates secondary metabolism regulator genes in Aspergillus flavus and shuts down aflatoxin production

• Published in: Scientific reports Vol. 12; no. 1; p. 5995
• Main Authors: Abbas, Asmaa, Wright, Colin W., El-Sawi, Nagwa, Yli-Mattila, Tapani, Malinen, Anssi M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.04.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326/193; 631/326/22/1292; 631/337/2019; Aflatoxin B1; Aflatoxin B1 - metabolism; Aflatoxins; Antioxidants; Aspergillus flavus; Aspergillus flavus - metabolism; Biosynthesis; Epicatechin; Flavonoids; Flavonoids - metabolism; Food additives; Fungicides; G protein-coupled receptors; Genes, Regulator; Humanities and Social Sciences; Kaempferol; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Methanol - metabolism; multidisciplinary; Phenolic compounds; Phenols; Plant Extracts - metabolism; Plant Extracts - pharmacology; Quercetin; Science; Science (multidisciplinary); Secondary Metabolism; Signal transduction; Toxins; Transcription; Zanthoxylum - genetics; Zanthoxylum bungeanum
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-09913-3

Aflatoxin B1 (AFB1) is a food-borne toxin produced by Aspergillus flavus and a few similar fungi. Natural anti-aflatoxigenic compounds are used as alternatives to chemical fungicides to prevent AFB1 accumulation. We found that a methanolic extract of the food additive Zanthoxylum bungeanum shuts down AFB1 production in A. flavus . A methanol sub-fraction (M20) showed the highest total phenolic/flavonoid content and the most potent antioxidant activity. Mass spectrometry analyses identified four flavonoids in M20: quercetin, epicatechin, kaempferol-3-O-rhamnoside, and hyperoside. The anti-aflatoxigenic potency of M20 (IC 50 : 2–4 µg/mL) was significantly higher than its anti-proliferation potency (IC 50 : 1800–1900 µg/mL). RNA-seq data indicated that M20 triggers significant transcriptional changes in 18 of 56 secondary metabolite pathways in A. flavus , including repression of the AFB1 biosynthesis pathway. Expression of aflR , the specific activator of the AFB1 pathway, was not changed by M20 treatment, suggesting that repression of the pathway is mediated by global regulators. Consistent with this, the Velvet complex, a prominent regulator of secondary metabolism and fungal development, was downregulated. Decreased expression of the conidial development regulators brlA and Medusa, genes that orchestrate redox responses, and GPCR/oxylipin-based signal transduction further suggests a broad cellular response to M20. Z. bungeanum extracts may facilitate the development of safe AFB1 control strategies.