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Title: COSY catalyses trans–cis isomerization and lactonization in the biosynthesis of coumarins

Abstract

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.

Authors:
 [1];  [1];  [1]; ORCiD logo [2];  [1];  [1];  [1];  [1];  [1];  [1];  [1]; ORCiD logo [3]; ORCiD logo [4];  [1]; ORCiD logo [2]; ORCiD logo [1]
  1. Ghent Univ., Ghent (Belgium); Vlaams Instituut voor Biotechnologie (VIB), Ghent (Belgium)
  2. Univ. of Wisconsin, Madison, WI (United States). Great Lakes Bioenergy Research Center
  3. Academia Sinica, Taipei (Taiwan); National Chung Hsing Univ., Taipei (Taiwan)
  4. Academia Sinica, Taipei (Taiwan); National Chung Hsing Univ., Taipei (Taiwan); National Taiwan Univ., Taipei (Taiwan)
Publication Date:
Research Org.:
Univ. of Wisconsin, Madison, WI (United States). Great Lakes Bioenergy Research Center
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1579532
Grant/Contract Number:  
SC0018409
Resource Type:
Accepted Manuscript
Journal Name:
Nature Plants
Additional Journal Information:
Journal Volume: 5; Journal Issue: 10; Journal ID: ISSN 2055-0278
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Vanholme, Ruben, Sundin, Lisa, Seetso, Keletso Carol, Kim, Hoon, Liu, Xinyu, Li, Jin, De Meester, Barbara, Hoengenaert, Lennart, Goeminne, Geert, Morreel, Kris, Haustraete, Jurgen, Tsai, Huei-Hsuan, Schmidt, Wolfgang, Vanholme, Bartel, Ralph, John, and Boerjan, Wout. COSY catalyses trans–cis isomerization and lactonization in the biosynthesis of coumarins. United States: N. p., 2019. Web. doi:10.1038/s41477-019-0510-0.
Vanholme, Ruben, Sundin, Lisa, Seetso, Keletso Carol, Kim, Hoon, Liu, Xinyu, Li, Jin, De Meester, Barbara, Hoengenaert, Lennart, Goeminne, Geert, Morreel, Kris, Haustraete, Jurgen, Tsai, Huei-Hsuan, Schmidt, Wolfgang, Vanholme, Bartel, Ralph, John, & Boerjan, Wout. COSY catalyses trans–cis isomerization and lactonization in the biosynthesis of coumarins. United States. doi:10.1038/s41477-019-0510-0.
Vanholme, Ruben, Sundin, Lisa, Seetso, Keletso Carol, Kim, Hoon, Liu, Xinyu, Li, Jin, De Meester, Barbara, Hoengenaert, Lennart, Goeminne, Geert, Morreel, Kris, Haustraete, Jurgen, Tsai, Huei-Hsuan, Schmidt, Wolfgang, Vanholme, Bartel, Ralph, John, and Boerjan, Wout. Mon . "COSY catalyses trans–cis isomerization and lactonization in the biosynthesis of coumarins". United States. doi:10.1038/s41477-019-0510-0.
@article{osti_1579532,
title = {COSY catalyses trans–cis isomerization and lactonization in the biosynthesis of coumarins},
author = {Vanholme, Ruben and Sundin, Lisa and Seetso, Keletso Carol and Kim, Hoon and Liu, Xinyu and Li, Jin and De Meester, Barbara and Hoengenaert, Lennart and Goeminne, Geert and Morreel, Kris and Haustraete, Jurgen and Tsai, Huei-Hsuan and Schmidt, Wolfgang and Vanholme, Bartel and Ralph, John and Boerjan, Wout},
abstractNote = {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.},
doi = {10.1038/s41477-019-0510-0},
journal = {Nature Plants},
number = 10,
volume = 5,
place = {United States},
year = {2019},
month = {9}
}

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