Study the biosynthesis pathway of 4-acetylantroquinonol B for improving submerged fermentation of Antrodia cinnamomea
Date Issued
2014
Date
2014
Author(s)
Yang, Shang-Han
Abstract
Antrodia cinnamomea (AC) is a treasured endemic Taiwanese medicinal mushroom. Its secondary metabolites possess many biological functions. Due to the fact that the fruiting body of AC grows very slow, the cultivation of mycelium by submerged fermentation is now a common practice for the production of bioactive compounds. The major bioactive compounds of AC are polysaccharides, triterpenes, diterpenes, succinic acid and maleic acid derivatives and ubiquinone. Previous study of our lab has purified 4-Acetylantroquinonol B (4-AAQB), an ubiquinone derivate, and proved that it is the major antiproliferative compound for hepatoma cells. 4-AAQB can mediate cell cycle arrest via decreases of CDK2 and CDK4 and increase p53, p21 and p27, and this lead to the proportion of cells in the G0/G1 phase increased, and that in the S phase decreased. The IC50 value of 4-acetylantroquinonol B toward HepG2 cells is 0.1 μg/mL. The objective of this study was to increase the production of 4-AAQB. Since the 4-AAQB is a kind of ubiquinone derivatives, this study referred the biosynthesis pathway and biological function of ubiquinone, and based on the three parts of the chemical structures of 4-acetylantroquinonol B, including Quinone ring, isoprenoid chain and γ-lactone, to investigate several possible precursors for increasing production of 4-acetylantroquinonol B. The results showed that 0.01% 4-hydroxybenzoic acid (3.7 mg/g dried mycelium), 0.01% CoQ0 (5.6 mg/g dried mycelium) and 0.01% CoQ10 (4.8 mg/g dried mycelium) supplementation could increase the 4-AAQB production possibly throughout the increase raw material needed for the construction of quinone ring. The 0.1% olive oil (3.0 mg/g dried mycelium), 0.1% oleic acid (3.6 mg/g dried mycelium) supplementation could increase the 4-AAQB production possibly by increasing the materials needed for biosynthesis of isoprenoid chain and γ-lactone. And from the cofactor of enzyme in the biosynthesis pathway, 0.1% MgSO4∙7H2O (6.5 mg/g dried mycelium) supplementation could also increase the amount of 4-acetylantroquinonol B. From the aforementioned results we can deduce that the biosynthesis between 4-acetylantroquinonol B and ubiquinone may be similar or closely related. Since AC can only grow on Cinnamomum kanehirai Hay, I chose two essential oils , α-terpeniol and geraniol from the host tree, and found that 0.01% α-terpeniol (2.7 mg/g dried mycelium) and geraniol (1.7 mg/g dried mycelium) supplementation could increase the synthesis of 4-AAQB. Finally, I combined the precursors from quinone ring and isoprenoid chain, and found that combined supplementation of 0.01% 4-hydroxybenzoic acid and 0.01% CoQ0 (27.8 mg/g dried mycelium)、0.01% 4-hydroxybenzoic acid and 0.1% oleic acid (5.1 mg/g dried mycelium) or 0.01% 4-hydroxybenzoic acid and 0.01% geraniol (3.9 mg/g dried mycelium), all had synergistic effect on the production of 4-acetylantroquinonol B.
Subjects
牛樟芝
ubiquinone
4-acetylantroquinonol B
4-hydroxybenzoic acid
CoQ0
CoQ10
oleic acid
Type
thesis
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