Design of CoQ10 crops based on evolutionary history

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.