Isoprenoid pathway

Since carotenoids are derived for the central isoprenoid pathway (Fig. 13.3), the regulation of their formation must involve a co-ordinated flux of isoprenoid imits into this branch of the pathway as well as into others such as the biosynthesis of sterols, gibberellins, phytol and terpenoid quinones. An imderstanding of the complexities of regulation of the pathway is necessary in order to target the regulatory steps for genetic manipulation. 

CHAPPELL J (1995) Biochemistry and molecular biology of the isoprenoid pathway in plants , Ann Rev Plant Physiol Plant Mol Biol, 46, 521-47. 

Subsequent cyclizations, dehydrogenations, oxidations, etc., lead to the individual naturally occurring carotenoids, but little is known about the biochemistry of the many interesting final structural modifications that give rise to the hundreds of diverse natural carotenoids. The carotenoids are isoprenoid compounds and are biosynthesised by a branch of the great isoprenoid pathway from the basic C5-terpenoid precursor, isopentenyl diphosphate (IPP). The entire biosynthesis takes place in the chloroplasts (in green tissues) or chromoplasts (in yellow to red tissues). 

Quinones represent a very large and heterogeneous class of biomolecules. Three major biosynthetic pathways contribute to the formations of various quinones. The aromatic skeletons of quinones can be synthesized by the polyketide pathway and by the shikimate pathway. The isoprenoid pathways are involved in the biosynthesis of the prenyl chain and in the formation of some benzoquinones and naphthoquinones. ... 

FIGURE 5.3.1 Parts of the isoprenoid pathways to carotenoids. 1 = MEP pathway. 2 = GGPP synthesis. 3 = Carotenoid biosynthetic pathway. 4 = Carotenoid degradative pathways. Enzyme abbreviations and enzyme activities are defined in Table 5.3.1. 

Hemmerlin, A. et al., A cytosolic Arabidopsis thaliana D-xylulose kinase catalyzes the phosphorylation of 1-deoxy-D-xylulose into a precursor of the plastidial isoprenoid pathway, Plant Physiol. 106, 86652, 2006. 

Wang, C.W., Oh, M.K., and Liao, J.C., Engineered isoprenoid pathway enhances astaxanthin production in Escherichia coli, Biotechnol. Bioeng. 62, 235, 1999. 

Rodriguez-Concepcion, M., Campos, N., Lois, L.M. et al. (2000) Genetic evidence of branching in the isoprenoid pathway for the production of isopentenyl diphosphate and dimethylallyl diphosphate in Escherichia coli. FEBS Letters, 473, 328-332. 

Bark beetles primarily utilize isoprenoid derived pheromones [100,101] and have been the most studied regarding their biosynthesis [8,98]. Earlier work indicated that the isoprenoid pheromones could be produced by the beetle altering host derived isoprenoids however more recent work indicates that for the most part bark beetles are producing pheromones de novo. The production of isoprenoids follows a pathway outlined in Fig. 4 which is similar to the isoprenoid pathway as it occurs in cholesterol synthesis in mammals. Insects cannot synthesize cholesterol but can synthesize farnesyl pyrophosphate. Insects apparently do not have the ability to cyclize the longer chain isoprenoid compounds into steroids. The key enzymes in the early steps of the isoprenoid... 

Triterpenoid saponins are synthesized via the isoprenoid pathway.4 The first committed step in triterpenoid saponin biosynthesis involves the cyclization of 2,3-oxidosqualene to one of a number of different potential products (Fig. 5.1).4,8 Most plant triterpenoid saponins are derived from oleanane or dammarane skeletons although lupanes are also common 4 This cyclization event forms a branchpoint with the sterol biosynthetic pathway in which 2,3-oxidosqualene is cyclized to cycloartenol in plants, or to lanosterol in animals and fungi. 

Ginsenosides are bios)mthesized via the isoprenoid pathway in the cytosol with mevalonic acid as the precursor for isopentenyl diphosphate (IFF) and dimethylallyl diphosphate (DMAPP), which are the two C5 starting units in the bios)mthesis of ginsenosides and other terpenoids... 

FIGURE 1.4 Proposed biosynthetic route for the biosynthesis of (A) squalene oxide (squalene-2,3-oxide) via the isoprenoid pathway and (B) triterpene saponins of the dammarane-type and oleanane-type from squalene oxide. PP, diphosphate group GPS, geranyl phosphate synthase FPS, farnesyl phosphate synthase NADPH, nicotinamide adenine dinucleotide phosphate. 

Carotenoids are lipid-soluble terpenoids derived from the isoprenoid pathway and are located in hydrophobic areas of cells. All have a 40-carbon isoprene backbone with a variety of ring structures at one or both ends (Fig. 8.2) [25]. The carbon skeleton is derived from five-carbon isoprenoid groups and contains alternating conjugated double bonds. There are two kinds of carotenoids (Fig. 8.2) carotenes composed of carbon and hydrogen and xanthophylls composed of carbon, hydrogen, and oxygen. 

Hugueney P, Bouvier F, Badfllo A, Quennemet J, d HarUngue A, Camara B (1996) Developmental and stress regulation of gene expression for plastid and cytosolic isoprenoid pathways in pepper fruits. Plant Physiol 111 619-626... 

Rubber is synthesized by plants via a side branch of the isoprenoid pathway by the enzyme rubber transferase (dy-prenyl transferase systematic name poly-dy-polyprenyl-diphosphate isopentenyl-diphosphate polyprenylcistransferase EC 2.5.1.20). Surprisingly, although this process has been studied for decades, due to the labile nature of the rubber transferase and the fact that it is a membrane-associated enzyme present in relatively low abundance, the identification of its protein subunits remain elusive. For some recent reviews on rubber biosynthesis, please refer to [248-251]. 

Fig. 11 Natural rubber is produced from a side branch of the ubiquitous isoprenoid pathway, with 3-hydroxy-methyl-glutaryl-CoA (HMG-CoA) as the key intermediate derived from acetyl-CoA by the general mevalonic-acid pathway. Mevalonate diphosphate decarboxylase (MPP-D) produces IPP, which is isomeiized to DMAPP by IPP isomerase (IPI). IPP is then condensed in several steps with DMAPP to produce GPP, FPP and GGPP by the action of a trani-prenyltransferase (TPT). The cA-l,4-polymeiization that yields natural rubber is catalyzed by cA-prenyltransferase (CPT), which uses the non-allylic IPP as substrate. Reprinted from [248], with permission from Elsevier...

Cell suspension cultures of Gypsophila paniculata and Saponaria officinalis produce very closely related triterpenoid saponins. Pretreatment of cell suspension cultures of G. paniculata with gypsogenin 3,0-glucuxonide (a triterpenoid saponin precursor in G. paniculata) followed by administration of [ C] acetate resulted in a marked reduction in incorporation of radioactivity into saponins and their precursors, but not into sterols and steryl glycosides [26]. Measurements of OSC activities revealed that there was no effect of elicitor treatment on CS levels in either species, but in G. paniculata AS levels went down while in S. officinalis they increased. This suggests that in these two species OSCs are regulating steps in the isoprenoid pathway and control the flux to sterols and triter-penes. 

In Tabernaemontana divaricata treatment of plant cell suspension cultures with an elicitor cause inhibition of CS activity [24,25]. This response is accompanied by stimulation of activity of constitutive enzyme activities of the isoprenoid pathway leading to 2,3-oxidosqualene (squalene synthase and squalene oxidase), and induction of enzymes required for biosynthesis of pentacyclic triterpenoid phytoalexins (/lAS and aAS). Thus inhibition of the branchpoint enzyme CS results in increased flux through the triterpenoid pathway. 

Figure 3.4. There are two routes known for the production of the basic Cj units used to form the isoprenoid/terpenoid carbon skeletons—the MVA and MEP isoprenoid pathways.

Figure 9.2. The inherent metabolic flexibility of the isoprenoid pathway leading to the synthesis of some carotenoid pigments. Genes coding for two enzymes capable of acting on carotenoid structures were introduced into Escherichia coli which had already been transformed to give it the capacity to make p,p-carotene. Both of the two introduced new enzymes (one shown with red arrows and the other with blue arrows) acted on multiple substrates because of their lack of specificity. The resulting matrix of transformations means that nine different products can be made by just two tailoring enzymes. (Adapted from Umeno et al. ° who used data from Misawa et al. °)...

Metabolites of the phylum Porifera account for almost 50% of the natural products reported from marine invertebrates. Of the 2609 poriferan metabolites, 98% are derived from amino acid, acetogenin, or isoprenoid pathways. Isoprenoids account for 50% of all sponge metabolites, while amino acid and polyketide pathways account for 26% and 22%, respectively. A significant number of sponge metabolites appear to be derived from mixed biosynthetic pathways. Most structures reported containing carbohydrate moieties were glycosides. 

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