Yap1p, the central regulator of the S. cerevisiae oxidative stress response, is activated by allicin, a natural oxidant and defence substance of garlic

Allicin is a thiol-reactive sulfur-containing natural product from garlic with a broad range of antimicrobial effects against prokaryotes and eukaryotes. Previous work showed that the S. cerevisiae OSI1 gene is highly induced by allicin and other thiol-reactive compounds, and in silico analysis revealed multiple Yap1p binding motifs in the OSI1 promoter sequence. An OSI1-promoter::luciferase reporter construct expressed in Wt and Delta yap1 cells showed absolute Yap1pdependence for allicin-induced OSI1-expression. A GFP::Yap1p fusion protein accumulated in the nucleus within 10 min of allicin treatment and Delta yap1 mutant was highly sensitive to allicin. Yap1p regulates glutathione (GSH) metabolism genes, and Delta gsh1,Delta gsh2 and Delta glr1 mutants showed increased sensitivity to allicin. Allicin activated the OSI1-promoter::luciferase reporter construct in Delta gpx3 and Delta ybp1 cells, indicating that allicin activates Yap1p directly rather than via H2O2 production. A systematic series of C-to-A Yap1p exchange mutants showed that the C-term C598 and C620 residues were necessary for allicin activation. These data suggest that Yap1p is an important transcriptional regulator for the resistance of yeast cells to allicin, and that activation occurs by direct modification of C-term cysteines as shown for other electrophiles.