Differential Regulation and Production of Secondary Metabolites among Isolates of the Fungal Wheat Pathogen Zymoseptoria tritici

The genome of the wheat-pathogenic fungus Zymoseptoria tritici represents extensive presence-absence variation in gene content. Here, we addressed variation in biosynthetic gene cluster (BGC) content and biochemical profiles among three isolates. We analyzed secondary metabolite properties based on genome, transcriptome, and metabolome data. The isolates represent highly distinct genome architecture but harbor similar repertoires of BGCs. Expression profiles for most BGCs show comparable patterns of regulation among the isolates, suggesting a conserved biochemical infection program. For all three isolates, we observed a strong upregulation of a putative abscisic acid (ABA) gene cluster during biotrophic host colonization, indicating that <i>Z. tritici</i> interferes with host defenses by the biosynthesis of this phytohormone. Further, during <i>in vitro</i> growth, the isolates show similar metabolomes congruent with the predicted BGC content. We assessed if secondary metabolite production is regulated by histone methylation using a mutant impaired in formation of facultative heterochromatin (H3K27me3). In contrast to other ascomycete fungi, chromatin modifications play a less prominent role in regulation of secondary metabolites. In summary, we show that <i>Z. tritici</i> has a conserved program of secondary metabolite production, contrasting with the immense variation in effector expression, and some of these metabolites might play a key role during host colonization. <b>IMPORTANCE</b> Zymoseptoria tritici is one of the most devastating pathogens of wheat. So far the molecular determinants of virulence and their regulation are poorly understood. Previous studies have focused on proteinaceous virulence factors and their extensive diversity. In this study, we focus on secondary metabolites produced by <i>Z. tritici</i>. Using a comparative framework, we characterize core and noncore metabolites produced by <i>Z. tritici</i> by combining genome, transcriptome, and metabolome data sets. Our findings indicate highly conserved biochemical profiles with contrasting genetic and phenotypic diversity of the field isolates investigated here. This discovery has relevance for future crop protection strategies.