ArticleNature communications2015
Emergence of terpene cyclization in Artemisia annua.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 77 citations in OpenAlex.
- Enhancing Enzyme Activity With Mutation Combinations Guided by Few-Shot Learning and Causal Inference.Angewandte Chemie (International ed. in English) · 2026Article
- Metabolomic and Single-Cell Transcriptomic Analyses Shed Light on Secondary Metabolite Profiling and Potential Developmental Dynamics of Glandular Trichomes in Artemisia argyi.Plant biotechnology journal · 2026Article
- Favorable epistasis in ancestral diterpene synthases promoted convergent evolution of a resin acid precursor in conifers.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Simulation-Guided Engineering Enables a Functional Switch in Selinadiene Synthase toward Hydroxylation.ACS catalysis · 2024Article
- Coevolutionary Information Captures Catalytic Functions and Reveals Divergent Roles of Terpene Synthase Interdomain Connections.Biochemistry · 2024Article
- Functional analysis of CYP71AV1 reveals the evolutionary landscape of artemisinin biosynthesis.Frontiers in plant science · 2024Article
- Active Site Loop Engineering Abolishes Water Capture in Hydroxylating Sesquiterpene Synthases.ACS catalysis · 2023Article
- Decoding Catalysis by Terpene Synthases.ACS catalysis · 2023Review
- Emergence of terpene chemical communication in insects: Evolutionary recruitment of isoprenoid metabolism.Protein science : a publication of the Protein Society · 2023Article
- A Single Active-Site Mutagenesis Confers Enhanced Activity and/or Changed Product Distribution to a Pentalenene Synthase fromBioengineering (Basel, Switzerland) · 2023Article
- Genetic analysis reveals the inconsistency of amorpha-4,11-diene synthase, a key enzyme in the artemisinin synthesis pathway, in asteraceae.Chinese medicine · 2023Article
- Mechanisms of protein evolution.Protein science : a publication of the Protein Society · 2022Review
- Toward improved terpenoids biosynthesis: strategies to enhance the capabilities of cell factories.Bioresources and bioprocessing · 2022Review
- Amorpha-4,11-diene synthase: a key enzyme in artemisinin biosynthesis and engineering.aBIOTECH · 2021Review
- Integrating structure-based machine learning and co-evolution to investigate specificity in plant sesquiterpene synthases.PLoS computational biology · 2021Article
- Terpene Synthases as Metabolic Gatekeepers in the Evolution of Plant Terpenoid Chemical Diversity.Frontiers in plant science · 2019Review
- De novo formation of an aggregation pheromone precursor by an isoprenyl diphosphate synthase-related terpene synthase in the harlequin bug.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Identification and characterization of a novel sesquiterpene synthase, 4-amorphen-11-ol synthase, fromPlant biotechnology (Tokyo, Japan) · 2018Article
- Bifurcatriol, a New Antiprotozoal Acyclic Diterpene from the Brown Alga Bifurcaria bifurcata.Marine drugs · 2017Article
- An in-silico insight into the substrate binding characteristics of the active site of amorpha-4, 11-diene synthase, a key enzyme in artemisinin biosynthesis.Journal of molecular modeling · 2017Article
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
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)-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.
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