BIOSYNTHESIS OF THE LABDANE DITERPENE MARRUBIIN IN MARRUBIUM VULGARE VIA A NON-MEVALONATE PATHWAY

The biosynthesis of the furanic labdane diterpene marrubiin has been s tudied in plantlets and shoot cultures of Marrubium vulgare (Lamiaceae ). The use of [2-C-14]acetate, [2-C-14]pyruvate, [2-C-14]mevalonic aci d and [U-C-14]glucose incorporation experiments showed that the labell ing of sterols in etiolated shoot cultures of M. vulgare was in accord ance with their biosynthesis via the acetate-mevalonate pathway. In co ntrast, the incorporation rates of these precursors into the diterpene marrubiin could not be explained by biosynthesis of this compound via the acetate-mevalonate pathway. Cultivation of etiolated shoot cultur es of M. vulgare on medium containing [1-C-13]glucose and subsequent C -13-NMR spectroscopy of marrubiin led to the conclusion that the biosy nthesis of marrubiin follows a non-mevalonate pathway. All isoprenic u nits of C-13-labelled marrubiin were enriched in those carbons that co rrespond to positions 1 and 5 of a putative precursor isopentenyl diph osphate. This labelling pattern from [1-C-13]glucose is consistent wit h an alternative pathway via trioses, which has already been shown to occur in Eubacteria and Gymnospermae. The labdane skeleton is a precur sor of many other skeletal types of diterpenes. Therefore it becomes o bvious that in connection with the few known examples of a non-mevalon ate pathway to isoprenoids the formation of some isoprenoids in plants via a non-mevalonate pathway might be quite common.