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Emergence of terpene cyclization in Artemisia annua

Salmon, Melissa, Laurendon, Caroline, Vardakou, Maria, Cheema, Jitender, Defernez, Marianne, Green, Sol, Faraldos, Juan Antonio and O'Maille, Paul E. 2015. Emergence of terpene cyclization in Artemisia annua. Nature Communications 6 , 6143. 10.1038/ncomms7143

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The emergence of terpene cyclization was critical to the evolutionary expansion of chemical diversity yet remains unexplored. Here we report the first discovery of an epistatic network of residues that controls the onset of terpene cyclization in Artemisia annua. We begin with ​amorpha-4,11-diene synthase (​ADS) and ​(E)-β-farnesene synthase (​BFS), a pair of terpene synthases that produce cyclic or linear terpenes, respectively. A library of ~27,000 enzymes is generated by breeding combinations of natural amino-acid substitutions from the cyclic into the linear producer. We discover one dominant mutation is sufficient to activate cyclization, and together with two additional residues comprise a network of strongly epistatic interactions that activate, suppress or reactivate cyclization. Remarkably, this epistatic network of equivalent residues also controls cyclization in a ​BFS homologue from Citrus junos. Fitness landscape analysis of mutational trajectories provides quantitative insights into a major epoch in specialized metabolism.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Publisher: Nature Publishing Group
ISSN: 2041-1723
Last Modified: 23 Mar 2017 03:25

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