Figure 1.

Coumarin biosynthetic pathway in plants. Simple coumarins, coumarin (1), umbelliferone (2), esculetin (3), and scopoletin (4) have modifications in their benzene ring. They are biosynthesized from the phenylpropanoid pathway via ortho-hydroxylation of cinnamate (10), p-coumarate (11), caffeate (12), and ferulate (13), respectively. The ortho-positions are shown by red arrows. Oxygen atoms introduced by ortho-hydroxylation are also highlighted in red. The ortho-hydroxylases from Arabidopsis (AtF6′H1), Ruta graveolens (RgC2′H), and Ipomoea batatas (Ib1 and Ib2) were functionally analyzed. AtF6′H1 and Ib1 catalyze ortho-hydroxylation of feruloyl-CoA (15), whereas RgC2′H and Ib2 were capable of reacting to both feruloyl-CoA (15) and p-coumaroyl-CoA (14) as the substrates. After hydroxylation, trans/cis isomerization and lactonization occur, resulting in the production of their respective coumarins. Umbelliferone (2) is a key intermediate of prenylcoumarin biosynthesis, from which furanocoumarins and pyranocoumarins (examples: psoralen and xanthyletin, respectively) are derived. No report has described cloning and functional analysis of the hydroxylases that introduce an ortho-hydroxy group to cinnamate and caffeate to form coumarin (1) and esculetin (3), respectively (hashed arrows). Coumarins substituted in the pyrone ring are thought to be derived from different pathways.