Dataset Information

Uncoupled activation and cyclisation in catmint reductive terpenoid biosynthesis

ABSTRACT: Terpenes synthases typically form complex molecular scaffolds by concerted activation and cyclization of linear starting materials in a single active site. We have determined that iridoid synthase, an atypical reductive terpene synthase, catalyses the activation of its substrate 8-oxogeranial into a reactive enol intermediate but does not catalyse the subsequent cyclisation into nepetalactol. This discovery led us to identify a class of nepetalactol-related short-chain dehydrogenase enzymes (NEPS) from catmint (Nepeta mussinii) which catalyse the stereoselective cyclisation of the enol intermediate into nepetalactol isomers. Subsequent oxidation of nepetalactols by NEPS1 provides nepetalactones, metabolites that are well known for both insect-repellent activity and euphoric effect in cats. Structural characterisation of the NEPS3 cyclase reveals it binds to NAD+ yet does not utilise it chemically for a non-oxidoreductive formal [4+2] cyclisation. These discoveries will complement metabolic reconstructions of iridoid and monoterpene indole alkaloid biosynthesis.

INSTRUMENT(S):

ORGANISM(S): Nepeta Mussinii

TISSUE(S): Plant Cell, Leaf, Trichome

SUBMITTER: Gerhard Saalbach

LAB HEAD: Sarah O'Connor

PROVIDER: PXD008704 | Pride | 2019-08-12

REPOSITORIES: Pride

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Uncoupled activation and cyclization in catmint reductive terpenoid biosynthesis.

Lichman Benjamin R BR Kamileen Mohamed O MO Titchiner Gabriel R GR Saalbach Gerhard G Stevenson Clare E M CEM Lawson David M DM O'Connor Sarah E SE

Nature chemical biology 20181210 1

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 (NE ...[more]

PMID: 30531909

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