作者: Melissa Salmon , Caroline Laurendon , Maria Vardakou , Jitender Cheema , Marianne Defernez
DOI: 10.1038/NCOMMS7143
关键词: Epistasis 、 Terpene 、 Chemical diversity 、 Botany 、 Enzyme 、 ATP synthase 、 Biology 、 Mutation 、 Artemisia annua 、 Stereochemistry
摘要: The emergence of terpene cyclization was critical to the evolutionary expansion chemical diversity yet remains unexplored. Here we report first discovery an epistatic network residues that controls onset in Artemisia annua. We begin with amorpha-4,11-diene synthase (ADS) and (E)-b-farnesene (BFS), a pair synthases produce cyclic or linear terpenes, respectively. A library B27,000 enzymes is generated by breeding combinations natural amino-acid substitutions from into producer. discover one dominant mutation sufficient activate cyclization, together two additional comprise strongly interactions activate, suppress reactivate cyclization. Remarkably, this equivalent also BFS homologue Citrus junos. Fitness landscape analysis mutational trajectories provides quantitative insights major epoch specialized metabolism.