Fig. 11
Proposed model for the regulation of penicillin biosynthesis and conidiation in response to oxidative stress by PcYap1 and PcRsmA. The model has been elaborated after the results obtained in this work complemented with previously published results with sufficient evidence to be applicable to this outline. In presence of naturally occurring or H2O2-generated ROS, PcYap1 undergoes conformational change, by direct sensing or mediated by peroxiredoxins (Prxs), and locates to the nucleus (see text). In these conditions, PcRsmA senses ROS, probably undergoes conformational change and locates to the nucleus by an unknown mechanism. PcYap1 binds a previously described regulatory sequence in the pcbAB gene promoter (TTAGTAA), while PcRsmA binds to a site 68 bp upstream from the PcYap1-binding site and to a second site in the penDE gene promoter. The two transcription factors positively regulate penicillin biosynthesis. PcRsmA positively regulates transcription of the Pc-yap1 gene. PcYap1 binds to an AP-1 site in the conidiation central regulatory pathway gene brlA and induces its transcription. PcRsmA also stimulates transcription of brlA, through direct (unproven) binding to the promoter or via regulation of Pc-yap1 transcription, or both. Upregulation of the brlA gene triggers conidiation. Both PcYap1 and PcRsmA participate in oxidative stress defense, reducing the amount of ROS in the cell; PcYap1 by directly controlling transcription of several oxidative stress response genes, and PcRsmA by putatively controlling expression of oxidative stress response genes or through regulation of Pc-yap1 transcription, or both. See text for additional details. Created with BioRender.com