Deletion of bZIP Transcription Factor <i>PratfA</i> Reveals Specialized Metabolites Potentially Regulating Stress Response in <i>Penicillium raistrickii</i>
2025
Anxin Zhang | Shu Zhang | Xinran Xu | Wen-Bing Yin
Fungal secondary metabolism (SM) is highly correlated with physiological processes that are typically regulated by pleiotropic regulators. In this study, we purposefully altered <i>PratfA</i>, a crucial regulator associated with oxidative stress in <i>Penicillium raistrickii</i> CGMCC 3.1066. After the knockout of <i>PratfA</i>, a novel polyketide (PK) raistrilide A (<b>1</b>) and the known nonribosomal peptide (NRP) tunicoidine (<b>2</b>) subsequently disappeared. Notably, compound <b>1</b> is a rare octaketone derivative and contains two unsubstituted <i>cis</i>-double bonds, demonstrating its unique biosynthetic mechanism. The knockout of <i>PratfA</i> resulted in the disappearance of <b>1</b>–<b>2</b> and greatly increased the susceptibility of Δ<i>PratfA</i> mutant strain to oxidative stress, rendering it nearly impossible to survive in such environments. At present, the <i>OE⸬PratfA</i> strain showed no phenotypic or oxidative stress sensitivity differences compared to the wild-type strain. Our findings highlight that the oxidative-stress-related transcription factor (TF) <i>PratfA</i> influences SM pathways in <i>P</i>. <i>raistrickii</i>. The manipulation of regulatory factors can guide the discovery of novel natural products (NPs).
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