Figure 2

Summary of FL enzymatic and transcription factor gene targets. Genes affected by fluconazole (FL) investigated in this study are enzymes along the ergosterol biosynthetic pathway (circles) and transcription factors directly regulated by sterol and heme levels (squares). ERG11, the gene that codes for lanosterol C-14-α demethylase, is the primary target of FL. CYP450 C-22 sterol desaturase, ERG5 (circle), is also a target of FL and its enzymatic activity is inhibited upon FL binding. FL’s nitrogen interacts with the heme groups of both Erg11p and Erg5p disrupting normal ergosterol synthesis and affecting downstream enzymatic reactions, including those performed by Δ[24]-sterol C-methyltransferase, Erg6p (circle). FL disruption of sterol biosynthesis additionally affects UPC2 (square), the gene that encodes for a sterol regulatory binding protein responsible for increased transcription of ERG genes upon sterol depletion. FL induces defective respiration due to its disruption of heme and oxygen levels. Therefore, HAP1 (square), a transcription factor responsible for regulating ERG11 expression under hypoxic conditions, is also targeted.