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Aokap9 gene knockout contributes to kojic acid synthesis in Aspergillus oryzae

Summary

Researchers discovered that removing the Aokap9 gene in the fungus Aspergillus oryzae doubles the production of kojic acid, a valuable chemical used in skin-whitening cosmetics and food preservation. By combining the Aokap9 gene removal with modifications to other genes (kojR and AozfA), they achieved even higher production levels. This research provides a practical pathway for creating high-yield strains that can produce kojic acid more efficiently for commercial applications.

Background

Kojic acid is a valuable secondary metabolite produced by Aspergillus oryzae with extensive applications in cosmetics, food, and pharmaceuticals. Despite its importance, many genes involved in kojic acid synthesis remain uncharacterized. Understanding the regulatory mechanisms governing kojic acid biosynthesis is essential for optimizing production.

Objective

To identify and characterize the Aokap9 gene and investigate its regulatory role in kojic acid synthesis. To elucidate the relationship between Aokap9 and key regulatory genes (kojR, laeA, AozfA) and explore the potential of Aokap9 as a target for metabolic engineering to enhance kojic acid production.

Results

Disruption of Aokap9 increased kojic acid production approximately twofold with elevated expression of kojA, kojR, and kojT. Mutations in kojR or laeA abolished kojic acid synthesis in Aokap9 mutants, establishing a regulatory pathway. AoZFA overexpression suppressed kojic acid accumulation in Aokap9 disruptants, while Δ Aokap9 Δ AozfA and Δ Aokap9-OE-kojR strains showed significantly enhanced kojic acid yields. Transcriptome analysis revealed AoKap9’s involvement in oxidative stress response through regulation of superoxide dismutase, catalase, and copper amine oxidase.

Conclusion

AoKap9 is a promising gene target for enhancing kojic acid production in A. oryzae through a regulatory pathway involving AoZFA, LaeA, and KojR. The findings provide valuable insights into kojic acid biosynthetic mechanisms and highlight the potential of combining Aokap9 disruption with other genetic modifications for developing high-yielding strains.
  • Published in:Microbial Cell Factories,
  • Study Type:Experimental Research,
  • Source: PMID: 41084052, DOI: 10.1186/s12934-025-02852-4
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