Uncoupled activation and cyclization in catmint reductive terpenoid biosynthesis
| Autor: | Gabriel R. Titchiner, Clare E. M. Stevenson, Sarah E. O'Connor, Mohamed O. Kamileen, David M. Lawson, Gerhard Saalbach, Benjamin R. Lichman |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Iridoid
medicine.drug_class Stereochemistry Reactive intermediate Dehydrogenase Crystallography X-Ray Cyclase Article 03 medical and health sciences chemistry.chemical_compound medicine Serine Nepetalactol Iridoids Molecular Biology 030304 developmental biology Plant Proteins 0303 health sciences Alkyl and Aryl Transferases Binding Sites biology Chemistry 030302 biochemistry & molecular biology Active site Cell Biology Bridged Bicyclo Compounds Heterocyclic Enol Cyclization biology.protein Monoterpenes Nepeta NAD+ kinase Oxidoreductases Oxidation-Reduction |
| ISSN: | 1552-4450 |
| Popis: | Terpene synthases typically form complex molecular scaffolds by concerted activation and cyclization of linear starting materials in a single enzyme active site. Here we show that iridoid synthase, an atypical reductive terpene synthase, catalyzes the activation of its substrate 8-oxogeranial into a reactive enol intermediate, but does not catalyze the subsequent cyclization into nepetalactol. This discovery led us to identify a class of nepetalactol-related short-chain dehydrogenase enzymes (NEPS) from catmint (Nepeta mussinii) that capture this reactive intermediate and catalyze the stereoselective cyclisation into distinct nepetalactol stereoisomers. Subsequent oxidation of nepetalactols by NEPS1 provides nepetalactones, metabolites that are well known for both insect-repellent activity and euphoric effects in cats. Structural characterization of the NEPS3 cyclase reveals that it binds to NAD+ yet does not utilize it chemically for a non-oxidoreductive formal [4 + 2] cyclization. These discoveries will complement metabolic reconstructions of iridoid and monoterpene indole alkaloid biosynthesis. A class of nepetalactol-related short-chain dehydrogenase/reductases (NEPS) captures a reactive enol intermediate produced by iridoid synthase for cyclization and subsequent oxidation into nepetalactones, the active ingredients in catnip. |
| Databáze: | OpenAIRE |
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