Fus3 Interacts with Gal83, Revealing the MAPK Crosstalk to Snf1/AMPK to Regulate Secondary Metabolic Substrates in Aspergillus flavus

Abstract

Aflatoxins (AFs), highly carcinogenic natural products, are produced by the secondary metabolism of fungi such as Aspergillus flavus. Essential for the fungi to respond to environmental changes and aflatoxin synthesis, the pheromone mitogenactivated protein kinase (MAPK) is a potential regulator of aflatoxin biosynthesis. However, the mechanism by which pheromone MAPK regulates aflatoxin biosynthesis is not clear. Here, we showed Gal83, a new target of Fus3, and identified the pheromone Fus3-MAPK signaling pathway as a regulator of the Snf1/AMPK energy-sensing pathway modulating aflatoxins synthesis substrates. The screening for Fus3 target proteins identified the β subunit of Snf1/AMPK complexes using tandem affinity purification and multiomics. This subunit physically interacted with Fus3 both in vivo and in vitro and received phosphorylation from Fus3. Although the transcript levels of aflatoxin synthesis genes were not noticeably downregulated in both gal83 and f us3 deletion mutant strains, the levels of aflatoxin B 1 and its synthesis substrates and gene expression levels of primary metabolizing enzymes were significantly reduced. This suggests that both the Fus3-MAPK and Snf1/AMPK pathways respond to energy signals. In conclusion, all the evidence unlocks a novel pathway of Fus3-MAPK to regulate AFs synthesis substrates by cross-talking with the Snf1/AMPK complexes.

Peanut Rhizosphere Achromobacter xylosoxidans Inhibits Aspergillus flavus Development and Aflatoxin Synthesis by Inducing Apoptosis through Targeting the Cell Membrane

“…Aspergillus flavus, a ubiquitous soil-borne saprophyte, presents a significant public health threat due to its ability to contaminate essential crops like peanuts, corn, and cotton, , and its potential to cause invasive aspergillosis in immunocompromised individuals. , This fungus attacks crops at both preharvest and postharvest stages, leading to substantial global economic losses . A particularly concerning aspect of A.…”