## 1 Introduction  
Species of Apiaceae are widely distributed in the Mediterranean area and elsewhere, where they are often used commercially as spices or drugs due to the presence of desirable specialized metabolites [1]. The most characteristic constituents of Apiaceae are coumarins and sesquiterpene lactones [2; 3; 4; 5], and also irregular terpenoids based on the thapsane carbon skeleton [6]. Several of the irregular terpenoids that have been found in Apiaceae have a structure that cannot be formed from the usual acyclic substrate molecules geranyl diphosphate (GPP, precursors to monoterpenoids), farnesyl diphosphate (FPP, precursors to sesquiterpenoids) and geranylgeranyl diphosphate (GGPP, precursors to diterpenoids) that are biosynthesized through head-tail fusion of IPP units, but are formed from tail-tail or head-head fused IPP units. The species studied here, _Thapsia laciniata_ [PERSON] (according to [PERSON] _et al._[7]), produces sesquiterpenoids based on the irregular thapsane carbon skeleton (Figure 1A), which has so far only been found in Apiaceae species. Thapsane-type sesquiterpenoids are thought to arise from the irregular terpene precursor, sesquilavandulyl diphosphate (SPP) [8], which itself is the product of an irregular farnesyl diphosphate synthase [9] that can perform one head-tail and one head-head fusion of the three IPP units giving rise to SPP. Only a few farnesyl diphosphate synthases making irregular precursors for the terpene synthases have been described so far, and this gene family therefore represents an unexploited area in the field of terpene biosynthesis and diversity [10; 11]. In addition to this class of irregular terpenoids, _Thapsia laciniata_ also contains regular sesquiterpenoids, such a guaianes, germacrenes, cadinenes, humulenes and hydroxylated derivatives thereof, such as oxy-caryophyllenes, and guaianolides (Figure 1B) [1; 4; 5]. The latter group includes thapsigargin, a major component and bioactive constituent of some _Thapsia_ species. Thapsigargin induces apoptosis in mammalian cells via a high affinity inhibition of the Sarco/endoplasmic reticulum Ca\({}^{2+}\) ATPase. Thapsigargins are currently valuable tools in the study of calcium homeostasis [6], and a derivative of a specific polyoxygenated sesquiterpene lactone from this class of compounds is currently undergoing clinical trials for the treatment of solid tumors [12]. While intensive chemotaxonomic studies have been performed on _Thapsia_ sp. in order to investigate the distribution of these specific highly bioactive thapsigargins, the mechanism of biosynthesis of thapsanes and guaianolides has not been elucidated. However, probable biochemical precursors such as hydrocarbon or oxygenated sesquiterpenes have previously been identified in several _Thapsia_ species [4; 5; 6; 13], and recently the first putative enzyme in thapsigargin biosynthesis was characterized from _Thapsia garganica_[14]. Additionally, research into the biosynthesis of sesquiterpene lactones from Asteraceae species, despite differences in their basic stereochemistry, provides a basis from which one can infer the likely mechanism of Apiaceae-type sesquiterpene lactone biosynthesis. In particular, a great deal of work has been carried out to elucidate the biosynthetic pathway of the anti-malaria drug artemisinin from _Artemisia annua_, demonstrating the involvement of a regular FPP synthase, a sesquiterpene synthase, at least one cytochrome P450 from the 71 clade, and aldehyde and alcohol dehydrogenases [15]. Further work on _Lactuca sativa_ has shown that the cytochromes P450 responsible for sesquiterpene hydroxylation are conserved, may be identified by phylogenetic analysis, but are likely to be promiscuous in their specificity for sesquiterpene substrates [16].