Oxygen vector accelerates farnesylation and redox reaction to promote the biosynthesis of 4-acetylantroquinonol B and antroquinonol during submerged fermentation of Antrodia cinnamomea

Abstract

4-Acetylantroquinonol B (4-AAQB) and antroquinonol (AQ) are the major benzoquinone compounds contributing to the anti-carcinoma effect of Antrodia cinnamomea. This study used oxygen vectors to increase the yields of 4-AAQB and AQ during the submerged fermentation of this pharmaceutical fungus. Incorporation of 5% of n-hexadecane in the culture medium increased the yields of 4-AAQB and AQ by 15.8-fold and 61.6-fold, respectively, as compared with the control group. During fermentation, the dissolved oxygen (DO) in the culture medium of both groups gradually decreased, but DO in the oxygen vector treated group maintained at 56.1% after 28 days of fermentation, which was approximately 2.2-fold of that in the control group (25.5%). HPLC-HRMS analysis revealed that this phenomenon could be attributed to the acceleration of farnesylation of the upstream compounds 5-DMQ0 and CoQ0 as well as the redox reaction of the benzoquinone ring of CoQ3B in the 4-AAQB and AQ biosynthetic pathways. Besides, a two-phase, in situ, liquid separation system was formed in the fermentation system. Extraction of 4-AAQB and AQ from the aqueous phase to the n-hexadecane hydrophobic phase could reduce the effect of back-inhibition and thus promote the biosynthesis of these two end products.