MYCOLab Ai Logo - gold and army green

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

Summary

Scientists discovered that a protein called PratfA controls the production of protective compounds in a fungus (Penicillium raistrickii) that help it survive stress. By removing this protein, they found two new natural products, including one with an unusual structure. The fungus without PratfA became very sensitive to oxidative stress and couldn’t survive well, showing that this protein is important for both making protective compounds and surviving harsh conditions.

Background

bZIP transcription factors are evolutionarily conserved regulators involved in stress responses across eukaryotes. The bZIP transcription factor PratfA in Penicillium raistrickii is associated with oxidative stress response. Manipulation of regulatory factors is an effective strategy for discovering novel secondary metabolites in fungi.

Objective

To investigate the role of the bZIP transcription factor PratfA in secondary metabolism and stress response in Penicillium raistrickii. To discover novel natural products through genetic manipulation of PratfA.

Results

Knockout of PratfA resulted in disappearance of raistrilide A (a novel octaketone polyketide) and tunicoidine (a nonribosomal peptide). The ΔPratfA mutant showed drastically increased susceptibility to oxidative stress (MSB, H2O2, diamide), rendering it nearly unable to survive. Raistrilide A is a rare octaketone derivative containing two unsubstituted cis-double bonds.

Conclusion

The bZIP transcription factor PratfA regulates secondary metabolite production in P. raistrickii and is critical for oxidative stress tolerance. Manipulation of PratfA successfully guided the discovery of a novel natural product with unique structural features. This study highlights the value of targeting regulatory factors for natural product discovery.
  • Published in:Journal of Fungi (Basel),
  • Study Type:Experimental Study,
  • Source: PMID: 39852491, DOI: 10.3390/jof11010072
Scroll to Top