Inverted stereocontrol of iridoid synthase in snapdragon

• Published in: The Journal of biological chemistry Vol. 292; no. 35; pp. 14659 - 14667
• Main Authors: Kries, Hajo, Kellner, Franziska, Kamileen, Mohamed Omar, O'Connor, Sarah E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2017; American Society for Biochemistry and Molecular Biology
• Subjects: Acyclic Monoterpenes; alcohol dehydrogenase (ADH); Alkyl and Aryl Transferases - chemistry; Alkyl and Aryl Transferases - genetics; Alkyl and Aryl Transferases - metabolism; Amino Acid Substitution; Antirrhinum - enzymology; Biocatalysis; Catalytic Domain; Catharanthus - enzymology; Enzymology; Iridoids - chemistry; Iridoids - metabolism; Models, Molecular; Molecular Structure; Monoterpenes - chemistry; Monoterpenes - metabolism; Mutation; NADP - chemistry; NADP - metabolism; natural product; natural product biosynthesis; Oxidation-Reduction; Phylogeny; plant biochemistry; Plant Proteins - chemistry; Plant Proteins - genetics; Plant Proteins - metabolism; Protein Conformation; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Stereoisomerism; Structural Homology, Protein; Substrate Specificity; Terpenes - chemistry; Terpenes - metabolism; terpenoid; natural product biosynthesis; terpenoid; alcohol dehydrogenase (ADH); plant biochemistry; natural product
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1074/jbc.M117.800979

The natural product class of iridoids, found in various species of flowering plants, harbors astonishing chemical complexity. The discovery of iridoid biosynthetic genes in the medicinal plant Catharanthus roseus has provided insight into the biosynthetic origins of this class of natural product. However, not all iridoids share the exact five- to six-bicyclic ring scaffold of the Catharanthus iridoids. For instance, iridoids in the ornamental flower snapdragon (Antirrhinum majus, Plantaginaceae family) are derived from the C7 epimer of this scaffold. Here we have cloned and characterized the iridoid synthase enzyme from A. majus (AmISY), the enzyme that is responsible for converting 8-oxogeranial into the bicyclic iridoid scaffold in a two-step reduction–cyclization sequence. Chiral analysis of the reaction products reveals that AmISY reduces C7 to generate the opposite stereoconfiguration in comparison with the Catharanthus homologue CrISY. The catalytic activity of AmISY thus explains the biosynthesis of 7-epi-iridoids in Antirrhinum and related genera. However, although the stereoselectivity of the reduction step catalyzed by AmISY is clear, in both AmISY and CrISY, the cyclization step produces a diastereomeric mixture. Although the reduction of 8-oxogeranial is clearly enzymatically catalyzed, the cyclization step appears to be subject to less stringent enzyme control.