Gene fusion and functional diversification of P450 genes facilitate thermophilic fungal adaptation to temperature change

Summary

Researchers discovered that a thermophilic fungus uses two special genes to adapt to temperature changes. One of these genes is uniquely fused from two different genes, creating a hybrid protein with multiple functions. These genes help the fungus produce iron-binding molecules that stabilize its structure and support its growth when temperatures drop, allowing the fungus to survive in environments from compost piles to stored grains.

Background

Thermophilic fungi adapt to high temperatures (45-60°C) and represent ideal models for studying fungal temperature adaptation mechanisms. Thermomyces dupontii produces prenylated indole alkaloids (PIAs) and their iron chelators through a gene cluster containing two P450 paralogs with previously unknown functions.

Objective

This study aimed to elucidate the specific roles of two P450 genes (P450S and P450L) in the biosynthesis of prenylated indole alkaloids, their iron chelators, and fungal adaptation to temperature reduction. The research examined genetic manipulation, metabolic profiling, and phenotypic analysis to characterize P450-mediated metabolic pathways.

Results

P450S catalyzes hydroxylation forming pyran rings in complex PPIAs and two hydroxamate cores in iron chelators. P450L, a unique gene fusion protein containing CYP64-like and FAD-binding domains, catalyzes dehydrogenation in complex PPIAs and forms a third hydroxamate core in novel iron chelators. Both genes facilitate pigmentation, conidiophore formation, and cell wall integrity during temperature reduction.

Conclusion

Gene fusion and functional diversification of P450 genes are critical mechanisms enabling thermophilic fungal adaptation to temperature changes. The P450-mediated metabolites regulate iron homeostasis and morphological development essential for fungal survival at reduced temperatures, demonstrating the ecological importance of P450-mediated secondary metabolism in temperature adaptation.
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