Two histone deacetylases, FfHda1 and FfHda2, are important for secondary metabolism and virulence in <em>Fusarium fujikuroi</em>.

Histone modifications are crucial for the regulation of secondary metabolism in various filamentous fungi. Here we studied the involvement of histone deacetylases (HDACs) in secondary metabolism in the phytopathogenic fungus Fusarium fujikuroi, a known producer of several secondary metabolites including phytohormones, pigments and mycotoxins. Deletion of three Zn(2+)-dependent HDAC-encoding genes, ffhda1, ffhda2 and ffhda4, indicated that FfHda1 and FfHda2 regulate secondary metabolism, whereas FfHda4 is involved in developmental processes but dispensable for secondary metabolite production in F. fujikuroi. Single deletions of ffhda1 and ffhda2 resulted not only in an increase or decrease, but also in derepression of metabolite biosynthesis under normally repressing conditions. Moreover, double deletion of both genes ffhda1 and ffhda2 shows additive but also distinct phenotypes with regard to secondary metabolite biosynthesis and both genes are required for GA-induced bakanae disease on the preferred host-plant rice, as &Delta;&Delta;ffhda1/ffhda2 mutants resemble the uninfected control plant. Microarray analysis with a &Delta;ffhda1 mutant that has lost the major HDAC revealed differential expression of secondary metabolite gene clusters subsequently verified by a combination of chemical and biological approaches. These results indicate that HDACs are not only involved in gene silencing but also in activation of some genes. Chromatin immunoprecipitation with &Delta;ffhda1 revealed significant alterations in the acetylation state of secondary metabolite gene clusters compared to the wild type thereby providing insights into the regulatory mechanism on chromatin level. Altogether, manipulation of HDAC-encoding genes constitutes a powerful tool to control secondary metabolism in filamentous fungi