Abstract
BACKGROUND: Triterpenoids derived from Sanghuangporus baumii exhibit significant pharmacological activities. However, their production remains limited due to the naturally low yield of triterpenoids and insufficient knowledge of the biosynthetic pathway. RESULTS: S. baumii strain DL102 was isolated, and the effects of Mn²(+) on its mycelial growth and metabolism were assessed. Treatment with 1 mM Mn²(+) significantly enhanced mycelial biomass accumulation, increasing by 0.42 g/L compared to the Mn0 group. This increase was associated with enhanced soluble sugar content and the upregulation of the expression of key metabolic genes. Furthermore, total triterpenoids content peaked at 10 mM Mn²(+) (28.7 ± 0.3 mg/g), representing a 2.03-fold increase relative to the Mn0 control group. This enhancement was primarily attributed to the activation of the terpenoid biosynthesis pathway, particularly through HMGS (3-hydroxy-3-methylglutaryl-CoA synthase) regulation by Mn²(+). The heterologous expression of HMGS in Saccharomyces cerevisiae resulted in the overexpression strain Sc-HS1, which exhibited significantly higher squalene production compared to the Ck strain, regardless of the presence or absence of an inducer. CONCLUSIONS: Our findings highlight the critical role of HMGS in triterpenoid biosynthesis under Mn²(+) treatment. These data provide a foundation for optimizing triterpenoids production, with potential applications in industrial-scale bioprocessing.