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Activation of Secondary Metabolism and Protease Activity Mechanisms in the Black Koji Mold Aspergillus luchuensis through Coculture with Animal Cells

Summary

Researchers found that growing koji mold (Aspergillus luchuensis) alongside mouse immune cells in the laboratory significantly increases the production of valuable bioactive compounds. The mold releases enzymes called proteases that break down proteins from the animal cells, which the fungus then uses as building blocks to create medicinal compounds. This discovery shows that coculturing microorganisms with animal cells is an effective strategy to unlock hidden chemical production capabilities in fungi, which could lead to new medicines and useful compounds.

Background

Koji molds like Aspergillus luchuensis are widely used in fermentation processes and possess numerous biosynthetic gene clusters, yet relatively few compounds have been isolated from them. Recent research has demonstrated that coculturing microorganisms with animal cells can stimulate secondary metabolism and bioactive compound production.

Objective

To evaluate whether coculturing koji molds with animal cells can activate secondary metabolism and enhance the production of bioactive compounds. The study investigated the mechanisms underlying this phenomenon and whether it extends beyond pathogenic microorganisms.

Results

Coculture of A. luchuensis with J774.1 cells markedly enhanced production of 8-hydroxy-3-carboxy-2-methylenenonanoic acid (1a and 1b) and 9-hydroxy-3-carboxy-2-methylenenonanoic acid (2) by 3.5-fold and 2.7-fold respectively. Mechanistic studies revealed that proteases secreted by the fungal strain degrade proteins from animal cells, which serve as precursors for secondary metabolite biosynthesis. First identification of compound 1b was achieved.

Conclusion

Coculturing koji molds with animal cells effectively activates secondary metabolism through protease-mediated degradation of secreted animal proteins. This strategy demonstrates the potential to enhance natural product production and has broader applications for non-pathogenic microorganisms in biotechnology.
  • Published in:ACS Omega,
  • Study Type:Experimental Study,
  • Source: PMID: 39464474, DOI: 10.1021/acsomega.4c07124
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