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

J Agric Food Chem. 2017 Jan 11;65(1):74-86. doi: 10.1021/acs.jafc.6b04346. Epub 2016 Dec 21.

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-13C]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 [13C2] fragments on the ring backbone were detected in the mass spectrum for [13C2]AQ, [13C2]4-AAQB, and their [13C2] 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.

Keywords: 4-acetylantroquinonol B; Antrodia cinnamomea; antroquinonol; orsellinic acid; polyketide pathway.

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / biosynthesis
  • 4-Butyrolactone / chemistry
  • Antrodia / chemistry
  • Antrodia / metabolism*
  • Biosynthetic Pathways
  • Cyclohexanones / chemistry
  • Fungal Proteins / metabolism
  • Molecular Structure
  • Mycelium / chemistry
  • Mycelium / metabolism
  • Polyketides / metabolism*
  • Resorcinols / metabolism*
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / biosynthesis
  • Ubiquinone / chemistry

Substances

  • Cyclohexanones
  • Fungal Proteins
  • Polyketides
  • Resorcinols
  • orsellinic acid
  • Ubiquinone
  • 4-acetylantroquinonol B
  • antroquinonol
  • 4-Butyrolactone