Design of CoQ10 crops based on evolutionary history

Cell. 2025 Apr 3;188(7):1941-1954.e15. doi: 10.1016/j.cell.2025.01.023. Epub 2025 Feb 13.

Abstract

Coenzyme Q (CoQ) is essential for energy production by mitochondrial respiration, and it is a supplement most often used to promote cardiovascular health. Humans make CoQ10, but cereals and some vegetable/fruit crops synthesize CoQ9 with a side chain of nine isoprene units. Engineering CoQ10 production in crops would benefit human health, but this is hindered by the fact that the specific residues of the enzyme Coq1 that control chain length are unknown. Based on an extensive investigation of the distribution of CoQ9 and CoQ10 in land plants and the associated Coq1 sequence variation, we identified key amino acid changes at the base of the Coq1 catalytic pocket that occurred independently in multiple angiosperm lineages and repeatedly drove CoQ9 formation. Guided by this knowledge, we used gene editing to modify the native Coq1 genes of rice and wheat to produce CoQ10, paving the way for developing additional dietary sources of CoQ10.

Keywords: coenzyme Q; crops; enzyme; genome editing; isoprenyl diphosphate synthase; land plants; nutrition; plant metabolism; rice.

MeSH terms

  • Alkyl and Aryl Transferases / chemistry
  • Alkyl and Aryl Transferases / genetics
  • Alkyl and Aryl Transferases / metabolism
  • Amino Acid Sequence
  • Crops, Agricultural* / genetics
  • Crops, Agricultural* / metabolism
  • Evolution, Molecular
  • Gene Editing
  • Humans
  • Oryza / genetics
  • Oryza / metabolism
  • Plant Proteins / chemistry
  • Plant Proteins / genetics
  • Plant Proteins / metabolism
  • Triticum / genetics
  • Triticum / metabolism
  • Ubiquinone* / analogs & derivatives
  • Ubiquinone* / biosynthesis
  • Ubiquinone* / chemistry
  • Ubiquinone* / genetics
  • Ubiquinone* / metabolism

Substances

  • Ubiquinone
  • coenzyme Q10
  • Alkyl and Aryl Transferases
  • ubiquinone 9
  • Plant Proteins
  • 4-hydroxybenzoate polyprenyltransferase