Pigment repression protects fungus from ferroptosis to maintain virulence

Fungal pathogens must adapt to host-derived stresses to establish infection, yet how secondary metabolite regulation contributes to this process remains poorly understood. Here, we show that Fusarium graminearum, a major cereal pathogen, suppresses the pigment aurofusarin biosynthetic gene cluster in response to host-derived iron excess, thereby preventing rubrofusarin-mediated ferroptosis and promoting invasive growth within wheat tissues. Rubrofusarin directly reacts with Fe²⁺ to form iron oxide complexes, resulting in intracellular iron accumulation, lipid peroxidation, and ferroptosis. Mechanistically, host-derived iron stress activates the HOG-MAPK pathway, leading to Hog1-dependent phosphorylation of the transcription factor FgSR. Phosphorylated FgSR recruits the histone deacetylase FgRpd3 to the aurofusarin biosynthetic gene cluster, establishing a repressive chromatin state that limits rubrofusarin production. Our findings reveal epigenetic repression of secondary metabolism as an adaptive strategy that enables fungal pathogens to withstand host-imposed iron stress, evade ferroptosis, and maintain virulence. The phytopathogenic fungus Fusarium graminearum produces a secondary metabolite, aurofusarin, at late stages during wheat infection. Here, the authors show how the biosynthesis of aurofusarin is regulated to avoid host-induced iron stress that results from the formation of iron complexes by an aurofusarin intermediate.