COSY catalyzes trans-cis isomerization and lactonization in the biosynthesis of coumarins

Coumarins or 1,2-benzopyrones comprise a large class of secondary metabolites ubiquitously found in the plant kingdom. In many plant species, coumarins are particularly important for iron acquisition and plant defense. Here we show that COUMARIN SYNTHASE (COSY) is a key enzyme in the biosynthesis of coumarins. Arabidopsis thaliana cosy mutants are strongly reduced in coumarin levels and accumulate o-hydroxyphenylpropanoids instead. Accordingly, cosy mutants have reduced iron content and show growth defects when grown under conditions where iron availability is limited. Recombinant COSY is able to produce umbelliferone, esculetin and scopoletin from their respective o-hydroxycinnamoyl-CoA thioesters via two reaction steps: a trans-cis isomerization followed by a lactonization. This conversion happens partially spontaneously and is catalyzed by light, which explains why the need for an enzyme for this conversion has been overlooked. The combined results show that COSY has an essential role in the biosynthesis of coumarins in organs that are shielded from light, such as roots. These findings provide routes to improving coumarin production in crops or via microbial fermentation.