Biosynthesis of Antroquinonol and 4-Acetylantroquinonol B via a Polyketide Pathway Using Orsellinic Acid as a Ring Precursor in Antrodia cinnamomea

Abstract

Antroquinonol (AQ) and 4-acetylantroquinonol B (4-AAQB), isolated from the mycelium of Antrodia cinnamomea, have a similar chemical backbone to coenzyme Q (CoQ). Based on the postulation that biosynthesis of both AQ and 4-AAQB in A. cinnamomea starts from the polyketide pathway, we cultivated this fungus in a culture medium containing [U-C]oleic acid, and then we analyzed the crude extracts of the mycelium using UHPLC-MS. We found that AQ and 4-AAQB follow similar biosynthetic sequences as CoQ. Obvious [C] fragments on the ring backbone were detected in the mass spectrum for [C]AQ, [C]4-AAQB, and their [C] intermediates found in this study. The orsellinic acid, formed from acetyl-CoA and malonyl-CoA via the polyketide pathway, was found to be a novel benzoquinone ring precursor for AQ and 4-AAQB. The identification of endogenously synthesized farnesylated intermediates allows us to postulate the routes of AQ and 4-AAQB biosynthesis in A. cinnamomea.

Enhancement of antroquinonol production during batch fermentation using pH control coupled with an oxygen vector

“…In yeast and fungi, the benzoic ring of CoQ was from p ‐hydroxybenzoic acid . Biosynthesis of 4‐acetylantroquinonol B and antroquinonol was related to the CoQ pathway in A. camphorata …”

“…Some studies have reported that CoQ 0 is considered an electron acceptor of the superoxide radical or a model for the quinone site in the bacterial photosynthetic reaction center . In A. camphorata , the carbocyclic core (CoQ 0 ) of antroquinonol could be synthesized via the polyketide pathway from malonyl‐CoA and acetyl‐CoA, and then sesquiterpene side chain and other chemical group were added by Coq2 – Coq6 genes . So, CoQ 0 is an efficient precursor for antroquinonol synthesis.…”

“…42 Biosynthesis of 4-acetylantroquinonol B and antroquinonol was related to the CoQ pathway in A. camphorata. 33 CoQ 0 is the only CoQ that lacks an isoprenoid group on the quinoid ring, a feature important for its physicochemical properties. 43 Some studies have reported that CoQ 0 is considered an electron acceptor of the superoxide radical or a model for the quinone site in the bacterial photosynthetic reaction center.…”

“…While Antroquinonol has a densely substituted six‐membered ring with its three contiguous stereocenters, and its synthesis requires long linear synthetic sequences (over 17 steps) and is not suitable for large‐scale production yet. Antroquinonol has a similar chemical backbone to coenzyme Q 0 (CoQ 0 , 2,3‐dimethoxy‐5‐methyl‐1,4‐benzoquinone) and it is biosynthesized via a polyketide pathway in the mycelium of Antrodia camphorata …”

“…Antroquinonol has a similar chemical backbone to coenzyme Q 0 (CoQ 0 , 2,3-dimethoxy-5-methyl-1,4-benzoquinone) and it is biosynthesized via a polyketide pathway in the mycelium of Antrodia camphorata. 33 The pH is one of the most important parameters affecting mycelial growth and formation of metabolic products. In general, pH can affect enzyme activity and nutrient availability as a result of charge changes in the cell membrane.…”