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

Nat Plants. 2019 Oct;5(10):1066-1075. doi: 10.1038/s41477-019-0510-0. Epub 2019 Sep 9.


Coumarins, also known as 1,2-benzopyrones, comprise a large class of secondary metabolites that are ubiquitously found throughout the plant kingdom. In many plant species, coumarins are particularly important for iron acquisition and plant defence. Here, we show that COUMARIN SYNTHASE (COSY) is a key enzyme in the biosynthesis of coumarins. Arabidopsis thaliana cosy mutants have strongly reduced levels of coumarin and accumulate o-hydroxyphenylpropanoids instead. Accordingly, cosy mutants have reduced iron content and show growth defects when grown under conditions in which there is a limited availability of iron. Recombinant COSY is able to produce umbelliferone, esculetin and scopoletin from their respective o-hydroxycinnamoyl-CoA thioesters by two reaction steps-a trans-cis isomerization followed by a lactonization. This conversion happens partially spontaneously and is catalysed 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 function 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 by microbial fermentation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Arabidopsis / enzymology*
  • Arabidopsis / genetics
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism*
  • Catalysis
  • Coumarins / metabolism*
  • Glycosides / biosynthesis
  • Isomerism
  • Mutation
  • Plant Roots / metabolism
  • Pregnenolone / analogs & derivatives
  • Pregnenolone / biosynthesis
  • Scopoletin / metabolism
  • Umbelliferones / biosynthesis


  • Arabidopsis Proteins
  • Coumarins
  • Glycosides
  • Umbelliferones
  • esculentin steroid
  • 7-hydroxycoumarin
  • Pregnenolone
  • Scopoletin