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Glucose-6-Phosphate Dehydrogenase Modulates Shiraia Hypocrellin A Biosynthesis Through ROS/NO Signaling in Response to Bamboo Polysaccharide Elicitation

Summary

Researchers discovered that a specific enzyme called glucose-6-phosphate dehydrogenase (G6PDH) controls the production of hypocrellin A, a powerful therapeutic compound found in Shiraia fungi. When bamboo polysaccharides are added to fungal cultures, they trigger G6PDH activity, which then increases the production of signaling molecules that boost hypocrellin A biosynthesis. This finding could lead to better ways to produce this promising cancer-fighting photosensitizer at industrial scales using simple, cost-effective methods.

Background

Hypocrellin A (HA) is a photodynamic perylenequinone pigment from Shiraia fruiting bodies with clinical applications in photodynamic therapy. Glucose-6-phosphate dehydrogenase (G6PDH) is the rate-limiting enzyme of the pentose phosphate pathway that produces NADPH. Understanding G6PDH’s role in HA biosynthesis regulation could enable improved production strategies.

Objective

This study aimed to elucidate the regulatory role of G6PDH in hypocrellin A biosynthesis in Shiraia sp. S9 in response to bamboo polysaccharide (BPS) elicitation. The research investigated how BPS elicitation upregulates G6PDH expression and activity and the subsequent effects on reactive oxygen species (ROS) and nitric oxide (NO) signaling pathways.

Results

Optimal BPS elicitation (100 mg/L on day 3) enhanced HA production to 428.1 mg/L, a 1.6-fold increase over controls. BPS significantly upregulated G6PDH expression and activity, concomitant with increased H2O2, O2•−, and NO generation. The G6PDH inhibitor glucosamine suppressed both ROS and NO production and reduced HA biosynthetic gene expression (PKS, Omef, MFS) by 15.6-83.2%. These results established G6PDH as a central regulator coordinating ROS/NO signaling in HA biosynthesis.

Conclusion

G6PDH acts as a central regulator of BPS-induced HA biosynthesis through NADPH-dependent ROS/NO signaling, revealing novel metabolic crosstalk between the pentose phosphate pathway and fungal perylenequinone biosynthesis. BPS elicitation presents a cost-effective, scalable biotechnological strategy for enhanced HA production in Shiraia mycelium cultures, with potential for industrial-scale applications.
  • Published in:Molecules,
  • Study Type:Experimental Study,
  • Source: PMID: 41157077, DOI: 10.3390/molecules30204060
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