Transcriptomic and Metabolomic Profiling of Heat Stress Responses and Ganoderic Acid Biosynthesis in Ganoderma lucidum.

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Citation abstract

Ganoderma lucidum (G. lucidum) produces ganoderic acids (GAs), which are pharmacologically important triterpenoids with hepatoprotective, anti-inflammatory, and immunomodulatory properties. In this work, we investigated the effect of acute heat stress (HS) on the enhancement of GA production, and scrutinized the underlying metabolic reorganization process. For this purpose, we integrated transcriptomics and metabolomics to characterize G. lucidum’s HS response in semi-submerged static culture at two timepoints: immediately post-stress (HS-A) and during recovery (HS-B) when GA accumulation peaked. HS suppressed growth and biomass but increased total GA content to 2.6 mg/100 mg dry weight. Transcriptomic analysis revealed 3,058 differentially expressed genes at HS-A and 582 at HS-B. At HS-A, tricarboxylic acid cycle (TCA), oxidative phosphorylation and ABC transporter genes were upregulated alongside heat shock proteins, while carbohydrate metabolism, pyruvate processing, sugar signaling, mevalonate (MVA) pathway genes and 18 of 21 GA-biosynthetic cytochrome P450s were downregulated. Seven epigenetic regulators displayed different expression patterns. At HS-B, lipid catabolism and fatty acid β-oxidation genes were upregulated, and the MVA pathway was reactivated. Metabolomic profiling identified 4,324 metabolites with 427 differentially accumulated, enriched in terpenoids, GAs, fatty acyls, steroids and amino acids. We also identified heat shock co-chaperone DNAJ1 as a regulatory hub correlated with terpenoid metabolism. This study suggests that temporally coordinated metabolic reorganization may enhance the secondary metabolite production.