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Energy Metabolism Enhance Perylenequinone Biosynthesis in Shiraia sp. Slf14 through Promoting Mitochondrial ROS Accumulation

Summary

Scientists studied two similar fungi to understand how one produces more of a beneficial compound called perylenequinones (PQs), which have medical uses against infections and cancer. They discovered that the high-producing strain uses energy more efficiently, which causes tiny structures in the cells called mitochondria to produce reactive molecules (ROS). These reactive molecules trigger the fungus to make more PQs as a protective response. By controlling these processes, researchers can potentially improve the production of this valuable medicine.

Background

Perylenequinones (PQs) are important natural compounds with antimicrobial, anticancer, and antiviral photodynamic therapeutic properties. Currently extracted from bamboo pathogenic fungi, submerged fermentation using Shiraia species has emerged as a promising alternative for PQ production. Understanding the molecular mechanisms regulating PQ biosynthesis is essential for enhancing production.

Objective

This study investigates the molecular mechanisms regulating perylenequinone biosynthesis by comparing the high-producing strain Shiraia sp. Slf14 with its low-PQ-producing mutant Slf14(w). The research aims to elucidate the relationship between energy metabolism, reactive oxygen species accumulation, and PQ synthesis.

Results

Strain Slf14 demonstrated higher energy metabolism, faster sugar consumption, and significantly elevated PQ production compared to Slf14(w). Transcriptome analysis revealed upregulation of genes involved in redox processes and energy metabolism in Slf14. ROS inhibitors reduced PQ production in Slf14 by 68-80%, while ROS promoters increased PQ production in Slf14(w) by 13-22 fold, establishing ROS as crucial for PQ biosynthesis.

Conclusion

Enhanced energy metabolism in Slf14 promotes mitochondrial ROS accumulation, which triggers activation of gene clusters responsible for perylenequinone synthesis. A positive feedback loop exists among energy metabolism, ROS levels, and PQ production, with mitochondria serving as the primary ROS source. These findings provide insights for optimizing PQ biosynthesis in fermentation processes.
  • Published in:International Journal of Molecular Sciences,
  • Study Type:Original Research,
  • Source: PMC11432641, PMID: 39337596, DOI: 10.3390/ijms251810113
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