Emergence of terpene cyclization in Artemisia annua

Salmon, Melissa, Laurendon, Caroline, Vardakou, Maria, Cheema, Jitender, Defernez, Marianne, Faraldos, Juan A. and O'Maille, Paul E. (2015) Emergence of terpene cyclization in Artemisia annua. Nature Communications, 6. ISSN 2041-1723

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Abstract

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)-b-farnesene synthase (BFS), a pair of terpene synthases that produce cyclic or linear terpenes, respectively. A library of B27,000 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
Additional Information:	This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Faculty \ School:	Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Biosciences Teaching and Education Research
Depositing User:	Pure Connector
Date Deposited:	24 Sep 2016 00:06
Last Modified:	20 Apr 2023 00:08
URI:	https://ueaeprints.uea.ac.uk/id/eprint/59809
DOI:	10.1038/ncomms7143

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