Deletion of bZIP Transcription Factor PratfA Reveals Specialized Metabolites Potentially Regulating Stress Response in Penicillium raistrickii

Fungal secondary metabolism (SM) is highly correlated with physiological processes that are typically regulated by pleiotropic regulators. In this study, we purposefully altered , a crucial regulator associated with oxidative stress in CGMCC 3.1066. After the knockout of , a novel polyketide (PK) raistrilide A ( ) and the known nonribosomal peptide (NRP) tunicoidine ( ) subsequently disappeared. Notably, compound is a rare octaketone derivative and contains two unsubstituted -double bonds, demonstrating its unique biosynthetic mechanism. The knockout of resulted in the disappearance of - and greatly increased the susceptibility of Δ mutant strain to oxidative stress, rendering it nearly impossible to survive in such environments. At present, the 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) influences SM pathways in . . The manipulation of regulatory factors can guide the discovery of novel natural products (NPs).