Understanding the Essential Metabolic Nodes in the Synthesis of 4-Acetylantroquinol B (4-AAQB) by Antrodia cinnamomea Using Transcriptomic Analysis

4-Acetylantroquinol B (4-AAQB) is a ubiquinone that has been shown to have multiple anticancer activities and is only found in the rare medicinal fungus A. cinnamomea in Taiwan. The large-scale production and application of 4-AAQB is thus limited due to the high host specificity, long production cycle, and low 4-AAQB content of A. cinnamomea. Additionally, the lack of molecular genetic studies on A. cinnamomea has hindered the study of the synthetic pathway of 4-AAQB. In this work, transcriptomic analysis was conducted to understand the essential metabolic nodes in the synthesis of 4-AAQB by A. cinnamomea based on the differences using glucose and fructose as carbon sources, respectively. The results showed that the glyoxylate and TCA cycle, terpenoid synthesis pathway, and the quinone ring modification pathway were clarified as the most significant factors associated with 4-AAQB synthesis. The enzymes ACS, ACU7, ACUE, GPS, PPT, P450, GEDA, YAT1, CAT2, and METXA in these pathways were the essential metabolic nodes in the synthesis of 4-AAQB. When fructose was used as the substrate, the expressions of these enzymes were upregulated, and the synthesis of some important intermediate metabolites was enhanced, thus promoting the accumulation of 4-AAQB. Our work understood the mechanism of fructose promoting the synthesis of 4-AAQB and identified the essential metabolic nodes which could provide the theoretical basis for the development of fermentation strategies to produce 4-AAQB by A. cinnamomea.