The mycotoxin zearalenone couples secondary metabolism to N -acetylglucosamine catabolism

Fungal secondary metabolites are often viewed as terminal products of specialized metabolism, yet how their production influences the physiology of the producing organism remains poorly understood. Here, we show that zearalenone (ZEA) production is functionally coupled to N -acetylglucosamine (GlcNAc) catabolism in Fusarium graminearum . Transcriptome profiling of a ZEB2 -overexpressing strain revealed enrichment of GlcNAc metabolic functions, and exogenous ZEA induced key catabolic genes independently of Zeb2. Among pathway components, NAG , encoding GlcNAc-6-phosphate deacetylase, was critical for GlcNAc utilization, and its loss caused severe GlcNAc-dependent growth inhibition. Genetic impairment of NAG was poorly tolerated under elevated ZEA pathway activity. Conversely, NAG overexpression increased tolerance to exogenous ZEA and alleviated the growth defect associated with ZEB2 overexpression. Together, these findings reveal a functional connection between secondary metabolite production and primary nutrient metabolism and suggest that ZEA-associated metabolic remodeling contributes to the fitness of the producing fungus.