Isopentenyl diphosphate, biosynthesis

LANGE, B.M., CROTEAU, R., Isopentenyl diphosphate biosynthesis via a mevalonate-independent pathway isopentenyl monophosphate kinase catalyzes the terminal enzymatic step, Proc. Natl. Acad. Sci. USA, 1999,96,13714-13719. 

Kuzuyama T, Takagi M, Takahashi S, Seto H (2000) Cloning and characterization of 1-deoxy-D-xylulose 5-phosphate synthase from Streptomyces sp. Strain CL190, which uses both the mevalonate and nonmevalonate pathways for isopentenyl diphosphate biosynthesis. J Bacteriol 182 891... 

R 274 W. Eisenreich, F. Rohdich and A. Bacher, Isopentenyl Diphosphate Biosynthesis via 1-Deoxyxylulose 5-Phosphate , p. 133... 

Two SN1 reactions occur during the biosynthesis of geraniol, a fragrant alcohol found in roses and used in perfumery. Geraniol biosynthesis begins with dissociation of dimethylallyl diphosphate to give an allylic carbocation, which reacts with isopentenyl diphosphate (Figure IT 15). From the viewpoint of isopentenyl diphosphate, the reaction is an electrophilic alkene addition, but from tile viewpoint of dimethylallyl diphosphate, the process in an Sjjl reaction in which the carbocation intermediate reacts with a double bond as the nucleophile. 

The mevalonate pathway for the biosynthesis of isopentenyl diphosphate from three molecules of acetyl CoA. Individual steps are explained in the text. 

Figure 27.8 An overview of terpenoid biosynthesis from isopentenyl diphosphate.

Diterpenoids are derived biosynthetically from geranylgeranyl diphosphate (GGPP), which is itself biosynthesized by reaction of farnesvl diphosphate with isopentenyl diphosphate. Show the structure of GGPP, and propose a mechanism for its biosynthesis horn FPP and IPP. 

KAJIWARA s, FRASER p D, KONDO K and MISAWA N (1997) Expressiou of an exogenous isopentenyl diphosphate isomerase gene enhances isoprenoid biosynthesis in Escherichia coli Biochem J, 324, 421-6. 

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). 

The biosynthesis of monoterpenes, the major components of peppermint essential oils, can be divided into four stages (Fig. 9.4). Stage 1 includes the formation of isopentenyl diphosphate (IPP) and dimethylallyl alcohol (DMAPP). In plants, two separate pathways are utilized for the synthesis of these universal C5 intermediates, with the cytosolic mevalonate pathway being responsible for the formation of sterols and certain sesquiterpenes, and the plastidial mevalonate-independent pathway being involved in the biosynthesis of isoprene, monoterpenes, certain sesquiterpenes, diterpenes, tetraterpenes, as well as the side chains of chlorophyll and plastoquinone.16 In peppermint oil gland secretory cells, however, the mevalonate pathway is blocked and the biosynthesis of monoterpenoid essential... 

Figure 9.4 Monoterpene biosynthesis in peppermint oil gland secretory cells. The enzymes involved in this pathway are (1) 1-deoxy-D-xylulose 5-phosphate synthase, (2) 2-C-methyl-D-erythritol 4-phosphate reductoisomerase, (3) 2-C-methyl-D-erythritol 4-phosphate cytidyltransferase, (4) 4-(cytidine 5 -diphospho)-2-C-methyl-D-erythritol kinase, (5) 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, (6) isopentenyl diphosphate isomerase, (7) geranyl diphosphate synthase, (8)...

McCASKILL, D., CROTEAU, R., Monoterpene and sesquiterpene biosynthesis in glandular trichomes of peppermint Mentha x piperita) rely exclusively on plastid-derived isopentenyl diphosphate, Planta, 1995,197,49-56. 

ROHMER, M., KNANI, M., SIMONIN, P., SUTTER, B., SAHM, H., Isoprenoid biosynthesis in bacteria a novel pathway for the early steps leading to isopentenyl diphosphate, Biochem. J., 1993,295, 517-524. 

Lichtenthaler HK, Rohmer M, Schwender J (1997) Two independent biochemical pathways for isopentenyl diphosphate and isoprenoid biosynthesis in higher plants. Physiol Plantarum... 

Fig. 2. Schematic representation of paclitaxel biosynthesis. Dimethylallyl-diphosphate and isopentenyl-diphosphate are condensed through geranylgeranyl diphosphate synthase activity to render geranylgeranyl-diphosphate (GGPP). GGPP is converted into taxa-4(5), 11 (12)-diene in a reaction catalyzed by the taxane synthase (TS). A series of reactions catalyzed by cytochrome P450 monoxygenases lead to the production of a taxane intermediate that is further converted to baccatin III through enzymes-driven oxidation and oxetane ring formation. The side chain moiety of paclitaxel is derived from L-phenylalanine. Three consecutive arrows mean multiple steps. Ac, acetyl Bz, benzoyl.

The second pathway leads from acetyl-CoA to isopentenyl diphosphate active iso-prene ), the basic component for the isoprenoids. Its biosynthesis is discussed in connection with biosynthesis of the isoprenoid, cholesterol (see p. 172). 

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]. 

The initial demonstration that isopentenyl diphosphate may be used in the biosynthesis of dolichol phosphate in animals and plants... 

In the 1970s the biosynthesis of cannabinoids was investigated with radiolabeling experiments. 14C-labeled mevalonate and malonate were shown to be incorporated into tetrahydrocannabinolic acid and cannabichromenic acid at very low rates (< 0.02%). Until 1990 the precursors of all terpenoids, isopentenyl diphosphate and dimethyl-allyl diphosphate were believed to be biosynthesized via the mevalonate pathway. Subsequent studies, however, proved that many plant terpenoids are biosynthesized via the recently discovered deoxyxylulose phosphate pathway (Eisenreich et al., 1998 Rohmer, 1999). It was shown that the Cio-terpenoid moiety of cannabinoids is biosynthesized entirely or predominantly (>98%) via this pathway (Fellermeister et al., 2001). The phenolic moiety is generated by a polyketide-type reaction sequence. 

The terpenes, carotenoids, steroids, and many other compounds arise in a direct way from the prenyl group of isopentenyl diphosphate (Fig. 22-1).16a Biosynthesis of this five-carbon branched unit from mevalonate has been discussed previously (Chapter 17, Fig. 17-19) and is briefly recapitulated in Fig. 22-1. Distinct isoenzymes of 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) in the liver produce HMG-CoA destined for formation of ketone bodies (Eq. 17-5) or mevalonate.7 8 A similar cytosolic enzyme is active in plants which, collectively, make more than 30,000 different isoprenoid compounds.910 However, many of these are formed by an alternative pathway that does not utilize mevalonate but starts with a thiamin diphosphate-dependent condensation of glyceraldehyde 3-phosphate with pyruvate (Figs. 22-1,22-2). 

Figure 22-2 The glyceraldehyde 3-phosphate pyruvate alternative pathway of isoprenoid biosynthesis. The intermediate 1-deoxyxylulose 5-phosphate may enter terpenes, vitamin B6, and thiamin. Isopentenyl diphosphate is shown as the final product, but the intermediate steps are uncertain. See Lange et al 2 ...

Until 1993, all terpenes were considered to be derived from the classical acetate/mevalonate pathway involving the condensation of three units of acetyl CoA to 3-hydroxy-3-methylglutaryl CoA, reduction of this intermediate to mevalonic acid and the conversion of the latter to the essential, biological isoprenoid unit, isopentenyl diphosphate (IPP) [17,18,15]. Recently, a totally different IPP biosynthesis was found to operate in certain eubacteria, green algae and higher plants. In this new pathway glyceradehyde-3-phosphate (GAP) and pyruvate are precursurs of isopentenyl diphosphate, but not acetyl-CoA and mevalonate [19,20]. So, an isoprene unit is derived from isopentenyl diphosphate, and can be formed via two alternative pathways, the mevalonate pathway (in eukaryotes) and the deoxyxylulose pathway in prokaryotes and plant plastids [16,19]. 

Figure 6.10 De novo biosynthesis of isoprenoid pheromone components by bark and ambrosia beetles through the mevalonate biosynthetic pathway. The end products are hemiterpenoid and monoterpenoid pheromone products common throughout the Scolytidae and Platypodidae (Figure 6.9A). The biosynthesis is regulated by juvenile hormone III (JH III), which is a sesquiterpenoid product of the same pathway. The stereochemistry of JH III is indicated as described in Schooley and Baker (1985). Although insects do not biosynthesize sterols de novo, they do produce a variety of derivatives of isopentenyl diphosphate, geranyl diphosphate, and farnesyl diphosphate. Figure adapted from Seybold and Tittiger (2003).

Figure 27 Four possible pathways for ABA biosynthesis. Open and closed circles show the 13C label from [1-13C]-d-glucose in the mevaloic acid pathway and the MEP pathway, respectively. DAP, dihydroxyacetone phosphate DXP, 1-deoxy-xylulose-5-phosphate FDP, farnesyl diphosphate GAP, glyceraldehyde-3-phosphate GGDP, geranylgeranyl diphosphate HMG-CoA, 3-hydroxy-3-methylglutaryl CoA IDP, isopentenyl diphosphate MEP, 2-C-methyl-D-erythritol-4-phosphate.

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