Hypoxia-induced downregulation of cAMP drives Ganoderic acid biosynthesis and restricts biofilm development in...

Hypoxia, as a widely prevalent environmental factor, profoundly influences the adaptability of filamentous fungi by regulating energy metabolism and developmental processes. Previous studies have shown that oxygen-limited conditions can induce biosynthesis of GAs. However, the regulatory network governing GA synthesis under hypoxia remains unclear. This study shows hypoxic stress decreases intracellular ATP and increases transcription of oxygen sensor ofd1, while inhibiting AC activity and reducing cAMP signaling. Reducing cAMP levels through pharmacological and genetic approaches enhances hypoxia-induced GAs accumulation, confirming cAMP's negative regulatory role in GA synthesis. Additionally, the study found that AC activation significantly accelerates biofilm formation and increases its thickness, indicating that cAMP signaling participates in hypoxic adaptation by positively regulating biofilm development. Thus, hypoxia coordinates GA biosynthesis and biofilm maturation through cAMP-dependent signaling in G. lucidum, revealing novel insights into the synergistic adaptation of metabolism and development under environmental stress.