The fungal plant pathogen, Fusarium graminearum, contains two genes, FgCPK1 and FgCPK2, encoding the catalytic subunits of cAMP-dependent protein kinase A. FgCPK1 and FgCPK2 are responsible for most of the PKA activities and have overlapping functions in various cellular processes in F. graminearum. The cpk1 cpk2 double mutant was significantly reduced in growth, rarely produced conidia, and was non-pathogenic. In this study, we found that the cpk1 cpk2 double mutant was unstable and produced fast-growing spontaneous sectors that were defective in plant infection. All spontaneous suppressor strains had mutations in FgSFL1, a transcription factor gene orthologous to SFL1 in yeast. Thirteen suppressor strains had non-sense mutations at Q501, three suppressor strains had frameshift mutations at W198, and five suppressor strains had mutations in the HSF binding domain of FgSfl1. Only one suppressor strain had both a non-synonymous mutation at H225 and a non-sense mutation at R490. We generated the SFL1 deletion mutant and found that it produced less than 2% of conidia than that of the wild-type strain PH-1. The sfl1 mutant was significantly reduced in the number of perithecia on carrot agar plates at 7 days post-fertilization (dpf). When incubated for more than 12 days, ascospore cirrhi were observed on the sfl1 mutant perithecia. The infection ability of the sfl1 deletion mutant was also obviously defective. Furthermore, we found that in addition to the S223 and S559 phosphorylation sites, FgSFL1 had another predicted phosphorylation site: T452. Interestingly, the S223 phosphorylation site was responsible for sexual reproduction, and the T452 phosphorylation site was responsible for growth and sexual reproduction. Only the S559 phosphorylation site was found to play an important role in conidiation, sexual reproduction, and infection. Overall, our results indicate that FgSFL1 and its conserved PKA phosphorylation sites are important for vegetative growth, conidiation, sexual reproduction, and pathogenesis in F. graminearum.

For optimal proteolytic function, the proteasome core (CP or 20S) must associate with activators. The cAMP-PKA pathway is reported to affect the activity of the proteasome in humans. However, the relationship between the proteasome and PKA is not well characterized. Our results showed that the major catalytic subunit Cpk1 was degraded without the protection of Pkr. Eleven (out of 67) pkr suppressors had FgBlm10 C-terminal truncation, one suppressor had an amino acid change mutation in the PRE6 ortholog (FGRRES_07282), and one in the PRE5 ortholog (FGRRES_05222). These mutations rescued the defects in growth and conidial morphology, Cpk1 stability, and PKA activities in the pkr mutant. The interaction of FgBlm10 with FgPre5 and FgPre6 were detected by co-immunoprecipitation, and the essential elements for their interaction were characterized, including the FgBlm10 C-terminus, amino acid D82 of FgPre6 and K62 of FgPre5. Additional FgBlm10-interacting proteins were identified in the wild type and pkr mutant, suggesting that PKA regulates the preference of FgBlm10-mediated proteasome assembly. In addition, PKA indirectly affected the phosphorylation of FgBlm10, and its localization in the nucleus. The truncation of the FgBlm10 C terminus also enhanced nuclear import and bleomycin resistance, suggesting its role in proteasome assembly at DNA damage sites. Collectively, our data demonstrated that regulation between PKA and proteasome degradation is critical for the vegetative growth of F. graminearum.

Histone acetylation, catalyzed by histone acetyltransferases (HATs) and reversed by histone deacetylases (HDACs), is a central epigenetic mechanism that regulates gene expression in eukaryotes. Identifying and characterizing these enzymes has rapidly advanced our understanding of this dynamic modification. In phytopathogenic fungi, HATs and HDACs modulate several cellular processes, including development, pathogenicity, and secondary metabolism. The filamentous fungus Fusarium graminearum causes Fusarium head blight, a destructive disease that reduces wheat yield and contaminates grain with the trichothecene mycotoxin deoxynivalenol (DON). Consequently, elucidating the regulatory networks that control fungal development, host colonization, and mycotoxin biosynthesis is essential for effective disease management. This review collates current knowledge on acetylation homeostasis in phytopathogenic fungi, with particular emphasis on F. graminearum, and evaluates evidence supporting a model wherein acetylation acts as a conditional regulatory hub rather than a universal transcriptional switch. Drawing on gene-deletion mutant analyses, large-scale acetylome profiling, and comparative genomics across multiple fungal species, we first cataloged the major HAT families—GNAT, MYST, CBP/p300, and TAF1—and HDAC families—Rpd3, Hos2, Hda1, and Sir2—and summarized the lysine acetylation and deacetylation sites they target, including H2BK11, H2BK16, H3K9, H3K14, H3K18, H3K23, H3K27, and H3K56. We then examine how acetylation homeostasis, defined as the dynamic balance between acetylation and deacetylation, regulates fungal morphogenesis, pathogenicity, and DON biosynthesis in F. graminearum, highlighting the functional interplay between HAT and HDAC complexes—exemplified by Gcn5 and Hos2 (Hdf1)—and their integration with cAMP–PKA and MAPK signaling cascades. We further analyzed how acetylation-dependent regulation intersected with proteasome-mediated protein stability, non-histone acetylation, and crosstalk with histone ubiquitination and methylation and assessed how acetylation responds to host-derived metabolites and microbial competitors, thereby extending its regulatory influence beyond canonical histone marks. Finally, comparative analyses across Magnaporthe oryzae, Aspergillus species, Botrytis cinerea, and Ustilago maydis reveal both conserved and species-specific roles of acetylation in pathogenicity. We conclude by advancing a refined conceptual model wherein acetylation operates not as a universal transcriptional on/off switch but as a conditional regulatory hub and is site-, locus-, and stage-specific and signal-responsive. Future studies that combine ChIP-seq, CUT&Tag, and multi-omics approaches will further clarify the direct molecular targets of HATs and HDACs and define their stage-specific activities during host colonization, thereby enabling the design of precise, pathogen-specific interventions. This framework offers new perspectives for developing targeted strategies to manage fungal diseases and reduce mycotoxin contamination.