Calcium-Induced Regulation of Sanghuangporus baumii Growth and the Biosynthesis of Its Triterpenoids

<i>Sanghuangporus baumii</i>, a fungus used in traditional Chinese medicine, produces important pharmacological compounds such as triterpenoids, but at levels significantly lower than those required for medical use. This study investigated the effects of various concentrations of Ca²⁺ on <i>S. baumii</i> mycelial growth and the heterologous biosynthesis of <i>S. baumii</i> triterpenoids. Under induction by 10 mM Ca²⁺, the growth rate (0.39 cm/d) and biomass (4.48 g/L) of <i>S. baumii</i> mycelia were 1.03% and 10.05% higher than those in the 0 mM Ca²⁺-treatment group, respectively. In contrast, 200 mM Ca²⁺ significantly inhibited the growth rate and biomass of the mycelia. Notably, the total triterpenoid content reached its peak (17.71 mg/g) in the 200 mM Ca²⁺-treatment group, with a significant increase in the Ca²⁺ content (3869.97 µg/g) in the mycelia. Subsequently, the differential metabolic pathways and related genes between the <i>S. baumii</i> groups were examined using transcriptomic analysis. The results indicated that the increase in the growth rate and biomass of <i>S. baumii</i> mycelia was primarily due to elevated soluble sugar content, whereas the growth inhibition was associated with the toxic effects of H₂O₂. The observed differences in triterpenoid content were mainly attributed to the activation of the terpenoid backbone biosynthesis pathway and the <i>AACT</i> gene. Finally, the <i>AACT</i> gene was cloned and transformed into yeast cells, thus creating strain Sc-AA1. Upon treatment at the optimal Ca²⁺ concentration, the squalene content of strain Sc-AA1 reached 0.78 mg/g, 2.89-fold higher than that in the control group. These findings are significant for the heterologous biosynthesis of triterpenoids from <i>S. baumii</i>. Our study demonstrates the feasibility of producing triterpenoids in <i>Saccharomyces cerevisiae</i> and provides a foundation for future optimization toward achieving industrially relevant yields.