Enhanced terpenoid synthesis in Alternaria alstroemeriae PPL7 via co-fermentation with Paeonia lactiflora roots:...

Total glucosides of paeony (TGP), primarily composed of monoterpene glycosides such as paeoniflorin and albiflorin, possess diverse pharmacological activities, including anti-inflammatory and neuroprotective effects. Traditional extraction from plants is limited by long growth cycles and low active content. This study employs an integrated metabolomics and transcriptomics strategy to systematically elucidate the molecular regulatory network underlying the biosynthesis of terpenoids by the Paeonia lactiflora leaf endophytic fungus Alternaria alstroemeriae PPL7 within a root co-fermentation system. Under the optimal root powder supplementation level (1.17%, w/v), the yield of target terpenoids increased significantly. Multi-omics comparative analysis revealed a global metabolic reprogramming induced by co-fermentation: the terpenoid backbone biosynthesis pathway was significantly enriched, and key terpenoid components (e.g., paeoniflorin) were upregulated. This was accompanied by fine-tuned flux regulation of the upstream mevalonate (MVA) pathway, enhanced precursor supply at mid-stream nodes, and metabolic diversion via protein prenylation. The synergistic activation of central carbon metabolism and amino acid degradation provided the necessary energy and reducing power for efficient terpenoid synthesis. This study not only elucidates the adaptive mechanisms by which endophytic fungi remodel their metabolic networks to efficiently synthesize plant-derived terpenoids but also provides novel strain resources and a theoretical basis for the sustainable manufacturing of terpenoid natural products using synthetic biology strategies.