ArticleNature2012
An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
133 citing papers in PubMed, 332 citations in OpenAlex.
- Antimicrobial and antibiofilm actions of iridoids: a comprehensive mechanistic review.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- tRNA-deacylase-directed discovery of biosynthetic pathways.Nature chemistry · 2026Article
- Propellane Alkaloid Biosynthesis and Total Synthesis via Interrupted Reaction Pathways.ACS central science · 2026Article
- Convergence and parallelism in the evolution of plant metabolism.Journal of integrative plant biology · 2026Review
- Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications.Chemical reviews · 2026Review
- Iridoids from Traditional Chinese Medicine for Neuropathic Pain: Therapeutic Potential and Molecular Mechanisms.Drug design, development and therapy · 2026Review
- Discovery of iridoid cyclase completes the iridoid pathway in asterids.Nature plants · 2025Article
- The missing link in the iridoid puzzle.Nature plants · 2025Article
- Single-cell metabolome and RNA-seq multiplexing on single plant cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Plant metabolism: Zoom in to the single-cell level.Plant physiology · 2025Review
- A Tight-Knit Family: The Medium-Chain Dehydrogenase/Reductases of Monoterpene Indole Alkaloid Biosynthesis.Biochemistry · 2025Review
- A Catalytic Asymmetric Intramolecular [4 + 1]-Cycloaddition for the Total Synthesis of Terpene Alkaloid Natural Products.Journal of the American Chemical Society · 2025Article
- Addressing the Evolution of Cardenolide Formation in Iridoid-Synthesizing Plants: Site-Directed Mutagenesis of PRISEs (Progesterone-5β-Reductase/Iridoid Synthase-like Enzymes) of Plantago Species.Molecules (Basel, Switzerland) · 2024Article
- Enhancing Substrate Preference of Iridoid Synthase via Focused Polarity-Steric Mutagenesis Scanning.Chem & bio engineering · 2024Article
- Article
- Transcriptome Analysis Provides Insights into Catalpol Biosynthesis in the Medicinal PlantGenes · 2024Article
- Engineered biosynthesis of plant heteroyohimbine and corynantheine alkaloids in Saccharomyces cerevisiae.Journal of industrial microbiology & biotechnology · 2024Article
- The leaf idioblastome of the medicinal plant Catharanthus roseus is associated with stress resistance and alkaloid metabolism.Journal of experimental botany · 2024Article
- Strategies on biosynthesis and production of bioactive compounds in medicinal plants.Chinese herbal medicines · 2024Review
- Protective effects of catalpol on cardio-cerebrovascular diseases: A comprehensive review.Journal of pharmaceutical analysis · 2023Review
73 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
The iridoids comprise a large family of distinctive bicyclic monoterpenes that possess a wide range of pharmacological activities, including anticancer, anti-inflammatory, antifungal and antibacterial activities. Additionally, certain iridoids are used as sex pheromones in agriculturally important species of aphids, a fact that has underpinned innovative and integrated pest management strategies. To harness the biotechnological potential of this natural product class, the enzymes involved in the biosynthetic pathway must be elucidated. Here we report the discovery of iridoid synthase, a plant-derived enzyme that generates the iridoid ring scaffold, as evidenced by biochemical assays, gene silencing, co-expression analysis and localization studies. In contrast to all known monoterpene cyclases, which use geranyl diphosphate as substrate and invoke a cationic intermediate, iridoid synthase uses the linear monoterpene 10-oxogeranial as substrate and probably couples an initial NAD(P)H-dependent reduction step with a subsequent cyclization step via a Diels-Alder cycloaddition or a Michael addition. Our results illustrate how a short-chain reductase was recruited as cyclase for the production of iridoids in medicinal plants. Furthermore, we highlight the prospects of using unrelated reductases to generate artificial cyclic scaffolds. Beyond the recognition of an alternative biochemical mechanism for the biosynthesis of cyclic terpenes, we anticipate that our work will enable the large-scale heterologous production of iridoids in plants and microorganisms for agricultural and pharmaceutical applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.